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Background: It is known that glycosidases and proteases are produced by the anaerobic gram-negative bacteria associated with bacterial vaginosis (BV). We hypothesized that these enzymes enzymatically degrade mucins, thereby destroying the mucus gel that otherwise helps protect against sexually transmitted pathogens, including HIV. Goal: The goal was to determine glycosidase and protease production by vaginal bacteria associated with BV and to compare these with symptoms and signs of abnormal discharge and to test vaginal fluid viscosity. Study Design: The anaerobic gram-negative rods recovered from the vaginas of 153 women with normal flora, intermediate flora, or BV were tested for production of sialidase, fucosidase, galactosidase, glucosaminidase, and glycine and arginine aminopeptidases. Results: Women with BV had higher frequencies and concentrations of bacteria producing mucin-degrading enzymes than did women with intermediate and normal flora (P < 0.001). Women with higher concentrations of bacteria producing mucin-degrading enzymes were more likely to have a thin discharge associated with BV (P < 0.001). The viscosity of diluted vaginal fluid samples from women with BV was significantly lower than those from women with normal flora (P = 0.001). Conclusion: These data support the hypothesis that BV organisms degrade the protective mucus gel.

Background: BufferGel is a novel spermicidal and microbicidal gel formulated to maintain the natural protective acidity of the vagina by acidifying semen, which otherwise alkalinizes the vagina. Goal: To test the efficacy of BufferGel for preventing sexually transmitted infections and pregnancy in animal models. Study Design: Animals were challenged with pathogens or sperm after pretreatment with both test and control agents, or after no pretreatment, then evaluated for infection or pregnancy using standard methods. Results: BufferGel provided significant contraceptive efficacy in the rabbit, and significant protection against vaginal and rectal transmission of herpes simplex virus type 2 (HSV-2) in the mouse, vaginal transmission of Chlamydia trachomatis in the mouse, and skin transmission of cottontail rabbit papillomavirus in the rabbit. It did not protect against vaginal transmission of Neisseria gonorrhoeae in the mouse. Conclusions: The protective efficacy of BufferGel in five of the six animal models suggests that this microbicide warrants clinical evaluation for both contraception and disease prevention.

Objectives: Tracking vaccine reactions and adverse events during a large-scale vaccination program such as the recent smallpox program or a pandemic flu outbreak will be a challenge. We report on vaccine reaction data collected using a novel telephone- and web-based electronic reporting system. The system was used to monitor vaccinees during the U.S. Army's smallpox vaccination campaign, which was part of the national program to prepare against biological attack. In addition, we report on the time course of events after smallpox vaccination based on the self-reported data and evaluate the validity and reliability of self-reported take information after smallpox vaccination.Methods: A prospective cohort of subjects receiving the smallpox vaccination volunteered to use an electronic monitoring system to track and report their vaccination reactions.Results: Users made 6.8 ± 6.2 (mean ± SD) reports using the electronic monitoring system. The sensitivity and positive predictive value of self-reported takes were high, 98.8% and 99.6%, respectively. The vaccination-site reactions progressed faster for revaccinees than first-time vaccinees.Conclusions: Simple-to-use telephone/Internet-based technology allowed detailed self-recording of response to smallpox vaccination among outpatients. Self-reports on site appearance were sufficient to determine vaccine takes in most vaccinees. During a mass vaccination event, an electronic monitoring system could facilitate tracking of vaccine reactions, including providing an early warning system for adverse events, and might reduce the burden associated with follow-up visits with healthcare professionals.

To determine whether or not large macromolecules and viruses can diffuse through mucus, we observed the motion of proteins, microspheres, and viruses in fresh samples of human cervical mucus using fluorescent recovery after photobleaching and multiple image photography. Two capsid virus-like particles, human papilloma virus (55nm, ∼20,000 kDa) and Norwalk virus (38nm, ∼10,000 kDa), as well as most of the globular proteins tested (15–650 kDa) diffused as rapidly in mucus as in saline. Electron microscopy of cervical mucus confirmed that the mesh spacing between mucin fibers is large enough (20–200nm) for small viruses to diffuse essentially unhindered through mucus. In contrast, herpes simplex virus (180nm) colocalized with strands of thick mucus, suggesting that herpes simplex virus, unlike the capsid virus particles, makes low-affinity bonds with mucins. Polystyrene microspheres (59–1000nm) bound more tightly to mucins, bundling them into thick cables. Although immunoglobulins are too small to be slowed by the mesh spacing between mucins, diffusion by IgM was slowed by mucus. Diffusion by IgM-Fc5μ, the Fc pentamer core of an IgM with all 10 Fab moieties removed, was comparably slowed by mucus. This suggests that the Fc moieties of antibodies make low-affinity bonds with mucins.