Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age

Abstract

Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of β-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1β-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1-to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.

Prevalence and factors associated with Trichomonas vaginalis infection in indigenous Brazilian women

“…Very few existing studies do not have enough data to describe the prevalence and associated factors for trichomoniasis and other STIs in this population [ 15 – 17 ]. Here, we observed a prevalence of 27.8% of the TV infection, which was dependent of laboratory diagnostic technique used [ 7 ]. Indeed, PCR (27.8%) and direct microscopy (7.41%) diagnosis showed a considerable difference in the prevalence of TV and might be due to factors, such as bacterial load and test sensitivity [ 18 ].…”

“…Although the Pap smear has specificity for T. vaginalis, there are sensitivity limitations that prevent the use of this technique for the diagnosis of infection [3,5]. The main focus of this technique is on the search for cellular changes such as atypical granular cells and squamous lesions, other findings such as Gardnerella vaginallis infection or Candida albicans, end up being in the background, which can also be related with problems in the female reproductive tract, especially the imbalance of bacterial flora, increasing the risk of infection by other STIs [6][7][8].…”

Cervicovaginal levels of human beta defensins during bacterial vaginosis

“…Corroborating our findings, Valore et al [ 17 ] demonstrated significant lower levels of hBD-1 and -2 in women presenting BV compared to healthy women. Recently, Fichorova et al [ 34 ] reported decrease of hBD-2 in Nugent scores of 4 to 6 and 7 to 10, although cervical immunity detectable within 3 months prior to cervicovaginal infection or dysbiosis showed higher hBD-2 levels. In contrast, Fan et al [ 28 ] reported an increase of vaginal hBD-2 in the presence of BV in non-pregnant women.…”

A Status of Cellular Immunity in Bacterial Dysbiosis and Bacterial Vaginosis

“…The fundamental possibility of predicting the development of dysbacteriosis and BV using math-ematical models of immunity disorders is justified by [22]. According to [23], the need to find optimal and simple prognostic models is an important modern problem, especially in the context of the tendency of BV to become chronic.…”