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Background Repeated C. trachomatis infections are common among young sexually active women. The relative frequency of re-infection and antibiotic treatment failure is undefined. Methods Adolescent women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessment every 3 months, including amplification tests for C. trachomatis, ompA genotyping and interviews and diary entries to document partner-specific coitus and event-specific condom use. Repeated infections were classified as re-infection or treatment failure using an algorithm. All infections with treatment outcomes were used to estimate antibiotic use-effectiveness. Results We observed 478 infection episodes among 210 participants; 176 women remained uninfected. Incidence rate was 34 per 100-woman years. Of those infected, 121 had ≥1 repeat infections forming 268 episode pairs; 183 pairs had complete data and were classified with the algorithm. Of repeated infections, 84.2% were definite, probable or possible re-infections, 13.7% were probable or possible treatment failures and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated a 92.2% treatment use-effectiveness. Conclusions Most repeat chlamydial infections in this high incidence cohort were re-infections, but treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies.

Haemophilus ducreyi causes chancroid, which facilitates transmission of HIV-1. To better understand the biology of H. ducreyi, we developed a human inoculation model. Here, we describe the clinical outcomes of 267 volunteers who were infected with H. ducreyi. There was a relationship between papule formation and dose. The outcome (pustule formation or resolution) of infected sites within a subject was not independent; the most important determinants of pustule formation were gender and host. When infected a second time, subjects (n = 41) segregated towards their initial outcome, confirming the host effect. Subjects with pustules developed local symptoms, requiring termination from the study after a mean of 8.6 days. Hypertrophic scars developed in 16.2% of volunteers who were biopsied, but the model was otherwise safe. Mutant-parent trials confirmed key features in H. ducreyi pathogenesis, and the model has provided an opportunity to study differential human susceptibility to a bacterial infection.

Because epithelial cells are the major cell type productively infected with Chlamydia during genital tract infections, the overall goal of our research was to understand the contribution of infected epithelial cells to the host defense. We previously showed that Toll-like receptor 3 (TLR3) is the critical pattern recognition receptor in oviduct epithelial (OE) cells that is stimulated during Chlamydia infection, resulting in the synthesis of beta interferon (IFN-␤). Here, we present data that implicates TLR3 in the expression of a multitude of other innate-inflammatory immune modulators including interleukin-6 (IL-6), CXCL10, CXCL16, and CCL5. We demonstrate that Chlamydia-induced expression of these cytokines is severely disrupted in TLR3-deficient OE cells, whereas Chlamydia replication in the TLR3-deficient cells is more efficient than in wild-type OE cells. Pretreatment of the TLR3-deficient OE cells with 50 U of IFN-␤/ml prior to infection diminished Chlamydia replication and restored the ability of Chlamydia infection to induce IL-6, CXCL10, and CCL5 expression in TLR3-deficient OE cells; however, CXCL16 induction was not restored by IFN-␤ preincubation. Our findings were corroborated in pathway-focused PCR arrays, which demonstrated a multitude of different inflammatory genes that were defectively regulated during Chlamydia infection of the TLR3-deficient OE cells, and we found that some of these genes were induced only when IFN-␤ was added prior to infection. Our OE cell data implicate TLR3 as an essential inducer of IFN-␤ and other inflammatory mediators by epithelial cells during Chlamydia infection and highlight the contribution of TLR3 to the inflammatory cytokine response.