Human Staphylococcus aureus (SA) nasal carriage provides a reservoir for the dissemination of infectious strains; however, factors regulating the establishment and persistence of nasal colonization are mostly unknown. We measured carriage duration and nasal fluid inflammatory markers after nasally inoculating healthy participants with their previously isolated SA strains. Ten out of 15 studies resulted in rapid clearance (9±6 days) that corresponded with upregulated chemokines, growth factors, and predominantly Th1-type cytokines, but not IL-17. Nasal SA persistence corresponded with elevated baseline levels of MIP-1β, IL-1β, and IL-6, no induction of inflammatory factors post-inoculation, and decreased IL-1RA:IL-1β ratio. SA-expressed staphylococcal protein A (SpA) levels correlated positively with carriage duration. Competitive inoculation studies revealed that isogenic SpA knockout (ΔSpA) strains were cleared faster than wild-type only in participants with upregulated inflammatory markers post-inoculation. The remaining participants did not mount an inflammatory response and did not clear either strain. ΔSpA strains demonstrated lower growth rates in carrier nasal fluids and lower survival rates when incubated with neutrophils. Collectively, the presented studies identify innate immune effectors that cooperatively modulate nasal carriage duration, and confirm SpA as a bacterial co-determinant of SA nasal carriage.

nasal carriage is transient in most humans and usually benign, but dissemination of to extranasal sites causes the majority of clinical infections, and is a major cause of serious infections in the United States. A better understanding of innate nasal decolonization mechanisms is urgently needed, as are relevant models for studying clearance. Here, we screened a population of healthy smokers for nasal carriage and compared the participants' abilities to clear experimentally applied nasal before and after completion of a smoking cessation program. We determined that cigarette smoking increases the mean nasal load (2.6 × 10 CFU/swab) compared to the load observed in healthy nonsmokers (1.7 × 10 CFU/swab) and might increase the rate of nasal carriage in otherwise-healthy adults: 22 of 99 smokers carried at the screening visit, while only 4 of 30 nonsmokers screened positive during the same time period. Only 6 of 19 experimental inoculation studies in active smokers resulted in clearance within the month of follow-up, while in the cessation group, 6 of 9 subjects cleared nasal and carriage duration averaged 21 ± 4 days. Smoking cessation associated with enhanced expression of -associated interleukin-1β (IL-1β) and granulocyte colony-stimulating factor (G-CSF) in nasal fluids. Participants who failed to clear exhibited a higher nasal load and elevated nasal interleukin-1 receptor antagonist (IL-1RA) expression at the preexperiment study visits. We conclude that smokers exhibit higher loads than nonsmokers and that innate immune pathways, including G-CSF expression and signaling through the IL-1 axis, are important mediators of nasal clearance.

The authors describe the initiation and use of a Web-based triage system in a college health setting. During the first 4 months of implementation, the system recorded 1,290 encounters. More women accessed the system (70%); the average age was 21.8 years. The Web-based triage system advised the majority of students to seek care within 24 hours; however, it recommended self-care management in 22.7% of encounters. Sore throat was the most frequent chief complaint (14.2%). A subset of 59 students received treatment at student health services after requesting an appointment via e-mail. The authors used kappa statistics to compare congruence between chief complaint and 24/7 WebMed classification (kappa = .94), between chief complaint and student health center diagnosis (kappa = .91), and between 24/7 WebMed classification and student health center diagnosis (kappa = .89). Initial evaluation showed high use and good accuracy of Web-based triage. This service provides education and advice to students about their health care concerns.

No abstract

Bacterial vaginosis (BV), a disorder of the female reproductive tract (FRT) in which a healthy Lactobacillus-dominant microflora is replaced by BV-associated bacteria (BVAB), can significantly increase the incidence of human immunodeficiency virus (HIV) acquisition. Discerning the effect of BV on the mucosal epithelium of the FRT may yield novel preventatives and therapeutics for HIV infection. Here, we investigated barrier dysfunction of the endocervix by host-derived factors, secreted in response to BV, as a potential cause of HIV infection. Using a polarized endocervical cell culture system, we determined that conditioned media (CM) from endocervical cells cocultured with BVAB (endocervical+BVAB CM), as well as cervicovaginal fluid (CVF) from women with BV, disrupted epithelial polarization. We assessed host matrix metalloproteinases (MMPs) as the BV-associated secreted factors which disrupt the endocervical epithelium. MMPs were overexpressed in endocervical+BVAB CM and CVF from women with BV and were capable of disrupting endocervical epithelial polarization. When we cocultured polarized endocervical cells with HIV-1-infected lymphocyte-derived cells, we discovered endocervical+BVAB CM and MMPs significantly increased the transmigration of virus through the epithelium, and treatment with an MMP inhibitor decreased these effects. When we examined the effect of CVF on HIV-1 transmigration through endocervical epithelium, we demonstrated that CVF samples with greater concentrations of BV-associated MMPs increased viral transmigration. Our results suggest MMPs increase HIV-1 infection by disrupting the endocervical epithelium, permitting transmigration of virus through the epithelium to infect underlying target cells.