Immunopathogenesis Of Chlamydia trachomatis Infection
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%. 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. We also we conducted a cost effectiveness study which modeled cost-effectiveness models analyses for screening males for chlamydia who were entering the National Job Core Training Program. It demonstrated that screening men in this venue prevented disease sequelae in current female partners, as well as future female partners. We have used the Internet to offer sampling for chlamydia for >1300 women at home using self-obtained vaginal swabs. Over 90% preferred to collect their own sample, with 96.7% indicating the collection was easy/very easy. Prevalence has been 15.3% in young women age 15-19 yr. Both young age and Black race were statistically associated with chlamydia positivity. We have extended Internet screening to males with self-collected penile swabs and urines. Overall, the chlamydia prevalence was 13.5% and 22.6% in men 15-19 yr. This unique public health strategy can help reach persons, who do not have insurance, prefer confidentiality and privacy, and who do not have a family doctor. We have documented a decrease in the prevalence of both chlamydia and gonorrhea in an out reach program for pregnant women in Baltimore. At the beginning of the screening program, the prevalence of chlamydia was 18.2% but declined over the subsequent years to 8.7% in 2008. The prevalence of gonorrhea also declined significantly from a high of 9.1% to a low of 1.3% in 2008. Continuation of outreach screening and treatment programs can help reduce the prevalence of STDs in our community. 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. Further studies are planned to access the ancillary effects of mass azithromycin therapy on other diseases, such as urogenital chlamydia and gonorrhea infections, diarrhea, acute respiratory diseases and malaria.
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