Analysis of Factors Driving Incident and Ascending Infection and the Role of Serum Antibody in<i>Chlamydia trachomatis</i>Genital Tract Infection

Russell, Ali N.; Zheng, Xiaojing; O’Connell, Catherine M.; Taylor, Brandie D.; Wiesenfeld, Harold C.; Hillier, Sharon L.; Zhong, Wujuan; Darville, Toni

doi:10.1093/infdis/jiv438

Cited by 52 publications

(75 citation statements)

References 38 publications

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“…TRAC identified risk factors for C. trachomatis and evaluated serum antichlamydia antibodies in association with chlamydial bacterial burden and incident infection 13. The data from the current study evaluated risk factors for M. genitalium and have not been presented previously.…”

Section: Methodsmentioning

confidence: 99%

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Risk factors for Mycoplasma genitalium endometritis and incident infection: a secondary data analysis of the T cell Response Against Chlamydia (TRAC) Study

et al. 2018

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Objective Assess risk factors for incident and endometrial Mycoplasma genitalium infection and determine if M. genitalium is associated with histological endometritis, an indicator of pelvic inflammatory disease. Methods This study was a secondary data analysis within the T cell Response Against Chlamydia (TRAC) Study, a prospective evaluation of 246 women withor at risk for Chlamydia trachomatis from urban outpatient clinics, who were followed quarterly for12 months. Risk factors for incident M. genitalium infection were determined by Cox regression. Relative risks were estimated by Poisson regression withrobust error measurements for models examining the association between M. genitalium and endometritis (histological evidence of plasma cells in endometrial stroma and neutrophils in the endometrial epithelium) and for models examining risk factors for detection of endometrial M. genitalium infection. Results M. genitalium prevalence was 16.7%, incidence was 25.3 per 100 person-years and 23% had repeated positive tests. Black race (non-black HRadj 0.4, 95% CI 0.2 to 0.9), less education (HRadj 2.4, 95% CI 1.2 to 5.1) and a new sexual partner (HRadj 3.1, 95% CI 1.7 to 5.4) were associated with incident M. genitalium. M. genitalium was associated with endometritis (RRadj 2.0, 95% CI 1.1 to 3.7). Trichomonas vaginalis (RRadj 2.0, 95% CI 1.2 to 3.4) and endometrial C. trachomatis (RRadj 1.7, 95% CI 1.1 to 2.8) were associated with endometrial M. genitalium. Conclusions M. genitalium is prevalent in women at high risk for C. trachomatis, persists over multiple follow-up visits and is associated with histological endometritis. Studies are needed to determine if screening for M. genitalium will improve reproductive outcomes.

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Section: Methodsmentioning

confidence: 99%

“…At enrolment, study personnel obtained demographic and medical history data, participants completed a self-reported questionnaire and cervical, vaginal and endometrial swab samples were obtained 13. Gram staining was used for bacterial vaginosis (BV) scoring by Amsel criteria 14.…”

Section: Methodsmentioning

confidence: 99%

Risk factors for Mycoplasma genitalium endometritis and incident infection: a secondary data analysis of the T cell Response Against Chlamydia (TRAC) Study

et al. 2018

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“…Diagnostic criteria included one or more of the following present on pelvic examination: cervical motion tenderness, or uterine tenderness or adnexal tenderness, in a sexually active young woman experiencing pelvic or lower abdominal pain (Workowski et al, 2015). The T cell Response Against Chlamydia (TRAC) cohort was comprised of asymptomatic women at high risk for STI (Russell et al, 2016). Both cohorts were recruited from clinics and emergency departments in Pittsburgh, PA.…”

Section: Methodsmentioning

confidence: 99%

“…Blood was collected for transcriptional profiling, and endometrial sampling was performed for microbiologic and histologic evaluation (Zheng et al, 2018); endometritis was defined according to published criteria (Kiviat et al, 1990). Chlamydial cervical burden was estimated via quantitative PCR using DNA extracted from reserved cervical swab eluates (Russell et al, 2016). The median cervical burden for the TRAC cohort = 10 4 genome equivalents/swab (Russell et al, 2016); high and low burden were defined as values above and below this level, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Chlamydial cervical burden was estimated via quantitative PCR using DNA extracted from reserved cervical swab eluates (Russell et al, 2016). The median cervical burden for the TRAC cohort = 10 4 genome equivalents/swab (Russell et al, 2016); high and low burden were defined as values above and below this level, respectively. For patients in TECH-N, clinical, cervical microbiological, and blood transcriptional data were collected, but endometrial biopsy was not performed.…”

Section: Methodsmentioning

confidence: 99%

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Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women

Zheng

O’Connell

Zhong

et al. 2018

Front. Cell. Infect. Microbiol.

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Sexually transmitted infection (STI) of the upper reproductive tract can result in inflammation and infertility. A biomarker of STI-induced upper tract inflammation would be significant as many women are asymptomatic and delayed treatment increases risk of sequelae. Blood mRNA from 111 women from three cohorts was profiled using microarray. Unsupervised analysis revealed a transcriptional profile that distinguished 9 cases of STI-induced endometritis from 18 with cervical STI or uninfected controls. Using a hybrid feature selection algorithm we identified 21 genes that yielded maximal classification accuracy within our training dataset. Predictive accuracy was evaluated using an independent testing dataset of 5 cases and 10 controls. Sensitivity was evaluated in a separate test set of 12 women with asymptomatic STI-induced endometritis in whom cervical burden was determined by PCR; and specificity in an additional test set of 15 uninfected women with pelvic pain due to unknown cause. Disease module preservation was assessed in 42 women with a clinical diagnosis of pelvic inflammatory disease (PID). We also tested the ability of the biomarker to discriminate STI-induced endometritis from other diseases. The biomarker was 86.7% (13/15) accurate in correctly distinguishing cases from controls in the testing dataset. Sensitivity was 83.3% (5/6) in women with high cervical Chlamydia trachomatis burden and asymptomatic endometritis, but 0% (0/6) in women with low burden. Specificity in patients with non-STI-induced pelvic pain was 86.7% (13/15). Disease modules were preserved in all 8 biomarker predicted cases. The 21-gene biomarker was highly discriminatory for systemic infections, lupus, and appendicitis, but wrongly predicted tuberculosis as STI-induced endometritis in 52.4%. A 21-gene biomarker can identify asymptomatic women with STI-induced endometritis that places them at risk for chronic disease development and discriminate STI-induced endometritis from non-STI pelvic pain and other diseases.

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Chlamydia trachomatis: Protective Adaptive Responses and Prospects for a Vaccine

Poston¹,

Darville²

2016

Biology of Chlamydia

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Chlamydia trachomatis is the most common cause of sexually transmitted bacterial infection globally. These infections translate to a significant public health burden, particularly women's healthcare costs due to serious disease sequelae such as pelvic inflammatory disease (PID), tubal factor infertility, chronic pelvic pain, and ectopic pregnancy. There is no evidence that natural immunity can provide complete, long-term protection necessary to prevent chronic pathology, making human vaccine development critical. Vaccine design will require careful consideration of protective versus pathological host-response mechanisms in concert with elucidation of optimal antigens and adjuvants. Evidence suggests that a Th1 response, facilitated by IFN-γ-producing CD4 T cells, will be instrumental in generating long-term, sterilizing immunity. Although the role of antibodies is not completely understood, they have exhibited a protective effect by enhancing chlamydial clearance. Future work will require investigation of broadly neutralizing antibodies and antibody-augmented cellular immunity to successfully design a vaccine that potently elicits both arms of the immune response. Sterilizing immunity is the ultimate goal. However, vaccine-induced partial immunity that prevents upper genital tract infection and inflammation would be cost-effective compared to current screening and treatment strategies. In this chapter, we examine evidence from animal and human studies demonstrating protective adaptive immune responses to Chlamydia and discuss future challenges and prospects for vaccine development.

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Analysis of Factors Driving Incident and Ascending Infection and the Role of Serum Antibody inChlamydia trachomatisGenital Tract Infection

Abstract: Serum anti-chlamydial IgG is not associated with a lowered rate of ascending or repeat infection. Identification of factors associated with ascending infection and increased risk of incident infection provide guidance for targeted screening of women at increased risk for sequelae.

Cited by 52 publications

References 38 publications

Risk factors for Mycoplasma genitalium endometritis and incident infection: a secondary data analysis of the T cell Response Against Chlamydia (TRAC) Study

Risk factors for Mycoplasma genitalium endometritis and incident infection: a secondary data analysis of the T cell Response Against Chlamydia (TRAC) Study

Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women

Chlamydia trachomatis: Protective Adaptive Responses and Prospects for a Vaccine

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