Immunopathogenesis Of Chlamydia trachomatis Infection

National Institute Of Allergy And Infectious Diseases

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Abstract

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world, causing serious complications on women's reproductive health including ectopic pregnancy, pelvic inflammatory disease and infertility. C. trachomatis also causes infection of the eye resulting in inflammation and in some cases blindness. The objectives of this project are to define the epidemiology, risk factors, transmission kinetics, and pathogenesis of C. trachomatis and other sexually transmitted infections an in different population settings, including populations in resource constrained countries. Chlamydia trachomatis is the most common nationally notifiable sexually transmitted infectious disease in the United States; however, the seroprevalence of C. trachomatis infection is unknown. This cross-sectional study was conducted among 1725 females aged 18-39 years who provided serum and urine samples in the 2013-2016 National Health and Nutrition Examination Surveys (NHANES). Presence of anti-C. trachomatis Pgp3 IgG was determined using both an enzyme-linked immunosorbent assay (ELISA) and multiplex bead array (MBA). Weighted seroprevalence estimates were calculated. In 2013-2016, overall seroprevalence of C. trachomatis Pgp3 IgG was 30.0% as measured by ELISA and 29.4%) as measured by the MBA assay. Overall agreement between tests was 87.1%. There was a high positive agreement by the MBA assay with current detection of chlamydia in urine (86%), a past-year diagnosis of chlamydia (82%), and a history of treatment for pelvic inflammatory disease (61%). Seroprevalence of C. trachomatis Pgp3 IgG, as measured by MBA, was significantly higher among non-Hispanic Blacks (68.0%), Mexican Americans (30.9%), and other Hispanics (35.0%) as compared to non-Hispanic Whites (21.4%). Seroprevalence was also associated with a higher lifetime number of sexual partners and a younger age at sexual debut. Both the ELISA and MBA serologic assays revealed a high prevalence of antibodies to C. trachomatis Pgp3 in young adult females in the U.S. household population. There were major racial/ethnic disparities in exposure to C. trachomatis, with increased vulnerability among non-Hispanic Blacks. Trachoma due to C. trachomatis infection is the most common cause of infectious blindness in the world. The WHO has recommended that three rounds of mass drug administration (MDA) with antibiotics be offered to control the disease in districts where the prevalence of follicular trachoma (TF) is >10% in children aged 1-9 years, with treatment coverage of at least 80%. We have conducted both surgical and antibiotic treatment intervention studies in Gambia, Niger, and Tanzania in efforts to control trachoma. However, the source of infection following mass treatment is often unknown. We sought to determine, in a cross-sectional survey of households of children with active trachoma, if we could detect the presence of Chlamydia trachomatis on household objects and on family members based on sleeping and caretaking patterns. In five villages in Kongwa, Tanzania, children <five years were randomly chosen for examination for trachoma, and households of all children with active trachoma were eligible for this study. Environmental swabs of bedding, furniture, clothing, and hands were taken and processed using Amplicor for detecting C. trachomatis DNA. The presence of an infant <1 year of age in the household, and whether the children's clothing had not been recently washed. C. trachomatis DNA is present in the environment of children with active trachoma, especially in households with an ocular infection. Specific findings also suggest that washing hands, clothing, and bedding may be important. There are limited nationally representative data on correlates of cytomegalovirus (CMV) shedding among children and adolescents. In addition, the genotype distribution of CMV infections has not been well characterized among general populations in the United States.We characterized urinary CMV shedding among CMV immunoglobulin G-positive 6- to 19-year-olds in the US household population using data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Prevalence of urinary CMV shedding was significantly lower among 9- to 11-year-olds (20.6%; aPR = 0.61; 95% CI, 0.44-0.83) and 12- to 19-year-olds (7.0%; aPR = 0.21; 95% CI, 0.14-0.30) compared with 6- to 8-year-olds (34.4%). Among CMV shedders, the youngest age group also had the highest urinary CMV viral loads. The prevalence of urinary CMV shedding among obese individuals was significantly lower compared with lean individuals (aPR = 0.68; 95% CI, 0.47-0.99). Among CMV shedders, glycoprotein B (gB)1 (51%) was the most prevalent gB variant, followed by gB2 (29%), gB3 (21%), and gB4 (13%); glycoprotein H (gH)2 (60%) was more prevalent than gH1 (48%). Multiple (2) gB (14%) and multiple gH (7%) infections were detected among CMV shedders. This study underscores the importance of young children even above the age of 5 years as a potential source of CMV transmission. The detection of multiple CMV strains among CMV shedders may have implications for the transmission of viral diversity as well as vaccine development. Several national guidelines consider illicit drug use as an indication for testing for some STIs. Sex-specific prevalence of T. vaginalis and/or C. trachomatis infection was examined by past-year marijuana use among 2958 sexually experienced, 20- to 39-year-old participants of the 2013-2016 National Health and Nutrition Examination Surveys. Past-year marijuana use was reported by 27.3% and 36.3% of females and males, respectively. Male and female past-year marijuana users were more likely to have new and multiple sexual partners in the past year (P < 0.05). Past-year marijuana use was associated with prevalent C. trachomatis and/or T. vaginalis infection among females (7.4% vs. 2.9%) and males (4.0% vs. 1.1). This association was attenuated after propensity score covariate adjustment among females and males. In conclusion, sexually transmitted infection prevalence was higher among persons with a past-year history of marijuana use; however, this association was not significant after accounting for measured confounders. Additional work is needed to characterize STI prevalence by the mode, duration, and frequency of marijuana. Although the FDA recently approved the human papillomavirus (HPV) vaccine for individuals aged 27-45 years, the CDC did not change its guidelines for routine HPV vaccination. Since recommendations for adult vaccination emphasize shared clinical decision-making based on risk of new infections, we examined the relationship between HPV prevalence and sexual behavior. This study was conducted among 5093 HPV-unvaccinated, sexually experienced adults aged 18-59 years in the National Health and Nutrition Examination Surveys (2013-2016). For each sex and age group, adjusted prevalences of 9-valent vaccine-specific, high-risk, and any HPV infection were estimated by number of lifetime sexual partners (LTSPs) using logistic regression. In each age group, genital HPV prevalence was higher among persons with >5 LTSPs compared with 1-5 LTSPs in both males and females. There were only slight reductions in HPV prevalence after removing participants who reported a new sexual partner in the past year. Prevalent HPV infection was primarily reflective of cumulative exposures over time (higher LTSPs). New exposures had limited impact, emphasizing the need to consider sexual history in the decision-making process for adult HPV vaccination.