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Microbicide efficacy and toxicity tests in a mouse model for vaginal transmission of Chlamydia trachomatis
Sharon L Achilles1, Priya B Shete, Kevin J Whaley
1The Johns Hopkins University, Baltimore, Maryland, USA.
Background:
Microbicides are being developed for woman-controlled protection against sexually transmitted diseases (STDs).
Goal:
The goal of the study was to test candidate microbicides in a mouse model for preventing vaginal transmission of and for acute toxicity to columnar epithelium.
Study Design:
Progestin-sensitized CF-1 mice were treated vaginally with 50 microl of microbicide, followed either by vaginal inoculation with 10 ID(50) of serovar D or by examination of the epithelial surface for acute toxicity with a viability stain (ethidium homodimer-1).
Results:
Nonoxynol-9 (N9), sodium dodecyl sulfate (SDS), chlorhexidine digluconate, and BufferGel all provided significant though incomplete protection against vaginal transmission. Other candidates, all of which were effective in vitro, provided no vaginal protection: kappa-carrageenan, dextran sulfate, polystyrene sulfonate, Concanavalin A, wheat germ agglutinin, and agglutinin. The surface-active agents (N9, SDS, and chlorhexidine) caused significant acute epithelial toxicity: 3 days after chlorhexidine exposure, mice also had vaginal friability and markedly increased susceptibility to. BufferGel was the only candidate tested that was both protective and relatively nontoxic.
Conclusion:
Microbicides can provide vaginal protection against in highly susceptible progestin-sensitized mice. Since N9 does not inactivate, it likely protects by killing target cells in the vagina. Despite the ability to both potently inactivate and kill target cells, two surface-active agents, SDS and chlorhexidine, failed to provide complete protection, a circumstance which emphasizes the importance of distributing microbicides to all susceptible surfaces.
Insights
Candidate microbicides offer protection against STDs in mice. BufferGel was the only protective and non-toxic option, highlighting the need for effective microbicide delivery.
Area of Science:
- Reproductive Health
- Infectious Disease Prevention
- Toxicology
Background:
- Developing woman-controlled microbicides is crucial for STD prevention.
- Existing microbicides require rigorous testing for efficacy and safety.
Purpose of the Study:
- To evaluate microbicide candidates for preventing vaginal STD transmission in a mouse model.
- To assess the acute toxicity of microbicides to vaginal columnar epithelium.
Main Methods:
- Progestin-sensitized mice received vaginal microbicide treatments.
- Mice were inoculated with STD pathogens or examined for epithelial toxicity using viability stains.
Main Results:
- Nonoxynol-9, sodium dodecyl sulfate, chlorhexidine, and BufferGel showed incomplete protection.
- Kappa-carrageenan and other candidates were ineffective in vivo despite in vitro activity.
- Surface-active agents caused significant epithelial toxicity; BufferGel was protective and relatively non-toxic.
Conclusions:
- Microbicides can protect against vaginal STD transmission in susceptible mice.
- Nonoxynol-9 likely protects by killing vaginal cells, not inactivation.
- Effective distribution of microbicides is essential for complete protection.