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The Chlamydia trachomatis plasmid and inclusion membrane protein CT135 are virulence factors in the pathogenesis of murine female genital tract infection. To determine if these virulence factors play a similar role in female nonhuman primates, we infected pig-tailed macaques with the same C. trachomatis strains shown to be important in the murine model. Wild-type C. trachomatis and its isogenic mutant strain deficient in both plasmid and CT135 were used to infect macaques. Macaques were given primary and repeated cervicovaginal challenges with the wild-type and mutant strains. The infection rate, infection duration, and antibody response were similar among macaques infected with both strains. Unexpectedly, colposcopy, laparoscopy, and histologic analysis revealed no substantial genital tract pathology following either primary or repeated cervicovaginal challenges. Cytokine analysis of cervicovaginal secretions from both challenged groups revealed low concentrations of interleukin 1β (IL-1β) and elevated levels of the interleukin 1 receptor agonist (IL-1RA). We propose that an imbalance of IL-1β and IL-1RA in macaques is the reason for the mild inflammatory responses observed in infected urogenital tissues. Thus, understanding the pathobiology of chlamydial infection requires a better understanding of host epigenetic and chlamydial genetic factors. Our findings also have implications for understanding the high frequency of asymptomatic infections in humans.

Background Nucleic acid-amplified tests for Chlamydia trachomatis are accurate but costly. Screening strategies for asymptomatic men are needed. Goal To assess C trachomatis screening strategies for asymptomatic males. Study Design Men attending a sexually transmitted disease clinic were tested for C trachomatis with ligase chain reaction and culture, and for urethral inflammation with urine leukocyte esterase and urethral Gram stain. Results C trachomatis prevalence was 5.5% among 1,625 asymptomatic men. Ligase chain reaction increased detection by 49% among men without urethral inflammation. An age of younger than 25 years and urethral inflammation were associated with positive ligase chain reaction results. The negative predictive value of urine leukocyte esterase was highest among older men, but urethral Gram stain was equally sensitive in predicting infection regardless of age. An age of younger than 30 years or urethral inflammation identified the highest proportion of infections (92%) and reduced the percentage of men screened by 43%. Conclusions Urine ligase chain reaction increased C trachomatis detection, particularly among men without urethral inflammation. Testing all asymptomatic men younger than 30 years is optimal, whereas negative urine leukocyte esterase or urethral Gram stain results in men 30 years or older support no testing.

Introduction Experimentally induced cervical chlamydial infection in the macaque may naturally cross-infect rectal epithelial cells which are also prone to Chlamydia trachomatis (CT) infection. This would be a significant finding in the field of STI preventive strategies, particularly when products intended for vaginal use are assessed for efficacy. If cross-infection does occur, it will be important to specifically assess rectal secretions for evidence of infection in vaginal product efficacy studies. Methods Twelve pigtailed macaques underwent direct cervical inoculation (1 mL C. trachomatis serovar E; 5E6IFU), followed by five weekly exams to detect infection in cervical and rectal secretions. Inoculant was delivered to the face of the cervix/vaginal fornix via 1 mL tuberculin syringe. Secretions were collected on dacron swabs. Chlamydial infection was detected at each site by culture and by nucleic acid amplification (NAAT: Aptima2) assays. Results Ten of twelve macaques tested positive for cervical chlamydial infection by culture and NAAT assays. The other two were transiently positive (2 weeks, 1 week) by NAAT only. All but three animals had chlamydial rRNA amplified from rectal swabs on at least one occasion. Five animals remained NAAT positive in rectal secretions for three weeks or more. One of these macaques had replicating chlamydia cultured from a rectal swab (week 3 only), followed by a spike in culture positivity from her next cervical sample (week4). Conclusion Experimental CT infection of the cervix indeed gave rise to chlamydia detection in rectal secretions in the majority of animals in this study. Culture positivity in cervical samples did not predict chlamydia detection in rectal samples. The paucity of culture positive results from rectal samples may be related to faecal contamination. Clearly it is advisable that rectal secretions be assessed for evidence of chlamydia in studies designed to assess prevention/treatment of cervical CT infections. Disclosure of interest statement This research was supported by NIH Contract Number HHSN272201000006I, Task Number HHSN27200008 and by the Office of Research Infrastructure Programs (ORIP) of the National Institutes of Health through Grant Number P51 OD010425 Washington National Primate Research Centre. No pharmaceutical grants were received in the development of this study.

We studied 95 women with uncomplicated Chlamydia trachomatis cervical infection. Quantitative isolation of C. trachomatis was performed in HeLa 229 cells, and the results were correlated with serum immunoglobulin M and immunoglobulin G antibody to the organism. We found that quantitative cultures for C. trachomatis can provide a meaningful measurement by which to evaluate the effect of the acquired immune response. In particular, secretory immunoglobulin A antibody to C. trachomatis in cervical secretion demonstrated a striking and inverse correlation with recovery of the organism from the cervix. It is suggested that this component of the immune response may regulate shedding of the organism.

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Chlamydia trachomatis is commonly found in the urethra of men with gonococcal urethritis. Studies report a 20%-40% rate of double infection. A two-year study of men attending a venereal disease clinic in California showed that only 4% (4/99) or 7% (10/147) of men with gonorrhea had concomitant chlamydial infection, whereas 25-31% of the men with nongonococcal urethritis (NGU) had chlamydial infection. Men with gonorrhea seemed to have substantial recent exposure to chlamydial infection, since C. trachomatis was isolated from the cervix of 20% (36/180) of female contacts. Microimmunofluorescence (micro IF) tests showed that 93.6% (131/141) of the men with gonorrhea had IgG antibodies to Chlamydia and 36% (51/141) had IgM antibodies. IgG antibody rates were higher than those found among men who had NGU or no urethritis (83% and 65%, respectively), a fact which suggests that in this clinic setting the men with gonorrhea had very high antecedent exposure to C. trachomatis and may have been resistant to reinfection.

Because few clinicians have access to laboratories offering cell culture confirmation of suspected Chlamydia trachomatis genital infections, we evaluated a diagnostic method in which fluorescein-conjugated monoclonal antibodies were used to directly identify C. trachomatis elementary bodies in slides made from genital secretions. Compared with culture results, the direct smear had a sensitivity of 92% and a specificity of 96% in 576 men, most of whom had symptoms and signs of urethritis. Among 595 women attending the same clinics, sensitivity of the direct smear for cervical infection was 89% and specificity was 99%. In 225 pregnant women screened in a prenatal or abortion clinic, the sensitivity and specificity of the test were 86% and 99% respectively. Direct detection of elementary bodies in genital smears offers an alternative diagnostic approach for C. trachomatis infections.