Immunopathogenesis Of Chlamydia trachomatis Infection

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Abstract

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world, causing serious adverse events on womens reproductive health including complications of pregnancy, pelvic inflammatory disease and infertility. The objectives of this project are to define the epidemiology, risk factors, transmission kinetics, and pathogenesis of C. trachomatis infections in different population settings and in different disease states. In a multi-center international trial of 5,000 participants, we screened for a variety of STDs using non-invasive molecular amplified assays. Prevalence of chlamydia in young women was 12.2% in China, 0.1% in India, 6.4% in Peru, 10.4% in Russia, and 2.5% in Zimbabwe. Gonorrhea prevalence was < 1.5% in all five countries. Serologic evidence for HSV-2 infection ranged from 9 to 20% among women in all countries except Zimbabwe, where the prevalence among women was 59%. These data have important implications for the future of the HIV epidemics because of the strong association of STDs, particularly HSV-2, for HIV acquisition. In a study screening high school students in Baltimore the overall prevalence for chlamydia was 18.1% of 957 students. Of those who tested positive for C. trachomatis the re-infection rate was 25.9%. These documented high repeat rates of chlamydia in Baltimore raise serious concerns about the resurgence of STDs among adolescents placing them at increased risk for HIV as well as other STDs. In conducting several cost-effectiveness analyses, we demonstrated that self-obtained vaginal swabs for nucleic acid amplification assays were the most cost effective method for preventing pelvic inflammatory disease. Vaginal specimen collection also received the highest preference rating by women. Screening high-risk men with partner notification also prevented more PID and was less costly than expanded screening for women. In an effort to further increase detection of chlamydia, we have also used the internet to offer screening for chlamydia to women at home using self-obtained vaginal swabs. From a total of 822 females who requested STD testing via the internet, the prevalence for chlamydia was 9.1%, gonorrhea 1.2%, and trichomonas 8.9%. We have subsequently extended internet screening to males with self-collected penile swabs and urines. Of 319 males the chlamydia prevalence was 27.1%. These studies demonstrate that internet recruitment of females and males for home sampling for STDs is feasible. With improved comprehensive screening we are beginning to document a decrease in the prevalence of both chlamydia and gonorrhea in pregnant and post-partum women in Baltimore. At the beginning of our screening programs, the prevalence of chlamydia in 1999 was 18.2% but declined over the subsequent years to 6.5% in 2007. Continuation of outreach screening programs can prove to be useful public health interventions in eventually reducing the prevalence of STDs in a community. With the implementation of microbicide clinical trials to prevent HIV infection, the potential inhibitory effects of these drugs should be carefully monitored in screening for C. trachomatis and N. gonorrhoeae. We measured the inhibitory effects of Buffergel, Pro2000, Tenofovir and placebo by nucleic acid amplification tests. Samples from Pro2000 showed inhibition at 5% concentration when tested for C. trachomatis and as low as 1% concentration for detection of N. gonorrhoeae. Buffergel, Tenofovir, and placebo showed no inhibition for chlamydia and variable inhibition at 5% and 2% concentrations for N. gonorrhoeae.[unreadable] To assess whether prostate cancer may be associated with chlamydia, HPV, or HHV-8 we participated in a multi-center study of 691 prostate cancer cases and an equal number of age-matched male controls. No associations were observed for either C. trachomatis, HPV-16, HPV-18, HPV-33 or any HPV antibody seropositivity and a significant inverse association was observed between HHV-8 antibody seropositivity and prostate cancer. Further studies are underway to examine the causal inverse association between HHV-8 infection and prostate cancer. We participated in surgical and antibiotic treatment intervention studies in Ethiopia, Niger, and Tanzania in efforts to control trachoma, the most common infectious cause of blindness worldwide. These studies have shown dramatic reductions in blindness in communities in which severe disease is first treated with surgery followed by community-wide azithromycin mass therapy. To determine whether infection recurs, we re-examined individuals in Tanzania five years after initiation of the program. Treatment coverage was 80% for all ages in the first year, although coverage 18 months later was lower at < 70%. At five years clinical trachoma rates were still lower than at baseline, ranging from 45% compared to 81% at baseline. Chlamydia infection rates at baseline were 71%, but declined to 27% five years after two rounds of mass therapy. Although mass treatment is associated with lower disease and infection rates in the long term, trachoma and C. trachomatis infection were not eliminated in this trachoma hyperendemic village. Continued implementation of combined surgical, antibiotic, and environmental interventions is needed.