Cervical Secretions Research Articles

Peritoneal contamination with ICG-stained cervical secretion as surrogate for potential cervical cancer tumor cell dissemination: A proof-of-principle study for laparoscopic hysterectomy.

Intracorporal colpotomy during radical hysterectomy for cervical cancer is discussed to be a risk factor for peritoneal dissemination of tumor cells. It might lead to increased recurrence rates after laparoscopic radical hysterectomy compared with abdominal hysterectomy, as shown by the recent LACC study. Data on the frequency or mechanisms of peritoneal contamination are missing. We aimed to analyze peritoneal contamination of cervical secretion during intracorporal colpotomy with a novel indocyaningreen (ICG)-based technique. In this prospective proof-of-principle study, patients undergoing routine laparoscopic or robot-assisted hysterectomy were selected. ICG was specifically applied to the cervical surface and routine surgery was performed. During colpotomy, pictures under white and fluorescence light were taken to evaluate frequency of contamination. By using cervically applied ICG we were able to visualize directly peritoneal contamination with cervical secretion during intracorporal colpotomy. We detected peritoneal contamination in 9/12 (75%) patients undergoing routine laparoscopic hysterectomy. Contamination of laparoscopic instruments occurred in 60% of the patients. When contamination occurred, it was routinely detectable during all steps of colpotomy. There were no adverse effects during surgery. Peritoneal contamination with cervical secretion frequently occurs during intracorporal colpotomy. This novel technique represents a promising tool for feasible and direct visualization of peritoneal contamination during colpotomy. The technique may be easily implemented in further studies on laparoscopic and abdominal hysterectomy and serve as a quality assessment tool for surgeons and surgical techniques.

Nanocarriers For Vaginal Drug Delivery.

Vaginal drug delivery approach represents one of the imperative strategies for local and systemic delivery of drugs. The peculiar dense vascular networks, mucus permeability, and range of physiological characteristics of the vaginal cavity have been exploited for therapeutic benefit. Furthermore, the vaginal drug delivery has been curtailed due to the influence of different physiological factors like acidic pH, constant cervical secretion, microflora, cyclic changes during periods along with turnover of mucus of varying thickness. This review highlights advancement of nanomedicine and its prospective progress towards the clinic. Relevant literature reports and patents related to topics are retrieved and used. The extensive literature search and patent revealed that nanocarriers are efficacious over conventional treatment approaches. Recently, nanotechnology based drug delivery approach has promised better therapeutic outcomes by providing enhanced permeation and sustained drug release activity. Different nanoplatforms based on drugs, peptides, proteins, antigens, hormones, nucleic material, and microbicides are gaining momentum for vaginal therapeutics.

Zika Fever: Development of Diagnostics, Prevention and Treatment

This review is devoted to the analysis of the literature data on the development of tools for diagnostics of Zika fever and detection of etiological agent – Zika virus (ZIKV) belonging to the Flaviviridae family. Preventive vaccines and antiviral drugs are also considered. RT-PCR method is critical for confirmation of Zika fever diagnosis. ZIKV RNA may be detected in blood serum, saliva, amniotic and cerebrospinal fluids, urine, semen, vaginal and cervical secretions. The duration of viremia in case of Zika fever is short; therefore the presence of ZIKV RNA in urine and sperm for up to 26 and 80 days, respectively, extends the time interval for the detection of this pathogen. Detection of IgM antibodies by serological methods is not a good reason to confirm a recent infection, since antibodies of this class, specific to flaviviruses, circulate in the bloodstream for more than 12 weeks. The IgM show high diagnostic value in confirmation of congenital infection only. There is a problem of differential diagnostics of flavivirus infections caused by antigenically related viruses that are dangerous for humans, for instance, Dengue, Yellow fever, West Nile fever viruses, tick-borne and Japanese encephalitis viruses. It is associated with the similarity of their genomes and, consequently, similar antigenic structure of viral proteins, structural glycoprotein E in particular. More reliable results can be obtained by using the nonstructural glycoprotein NS1, produced by molecular biology methods, as an antigen for the detection of specific antibodies. This viral protein can also be used in serological tests, as a clinical indicator in case of acute Zika fever. Forty five types of candidate vaccines against ZIKV, such as inactivated, live attenuated, recombinant, peptide, recombinant DNA and RNA-based, virus-vector and virus-like particle ones were designed and studied. It was established that their protective efficacy is mediated by induced antibodies, specific to structural glycoprotein E which initiates receptor binding and fusion with the membranes of infected cells. Currently, there is no licensed preparation for treating patients with flaviviral infections. Various drugs are screened, both with known antiviral effect and approved for use in clinical practice, and new compounds that inhibit the penetration of viral particles into host cells (structural glycoprotein E being the target) and virus replication (targets are NS5, NS2B nonstructural proteins).

Cervical and systemic concentrations of long acting hormonal contraceptive (LARC) progestins depend on delivery method: Implications for the study of HIV transmission.

Progestin-only long-acting reversible contraceptives (LARCs) are increasingly popular among women seeking contraception; however, recent epidemiological studies suggest that systemically administered medroxyprogesterone acetate (MPA) may increase HIV acquisition. In order to determine the exact mechanisms underlying increases in transmission specific to MPA use and to test safer, alternative contraceptive progestin types and delivery methods, in vitro modeling studies must be performed. To achieve this, it is imperative that accurate hormone concentrations be utilized when modeling progestin-mediated outcomes, as the down-stream effects are dose-dependent. The local concentrations of progestins to which the lower female genital tract tissues are exposed after initiation of LARCs are unknown, but they likely differ from peripheral concentrations, dependent upon the progestin type and delivery method. Here, we measured in vivo endocervical and plasma concentrations of (1) systemically-delivered depo MPA (DMPA), (2) levonorgestrel (LNG) delivered via intrauterine system (IUS) and (3) etonogestrel (ETG) delivered via vaginal ring in women who recently initiated contraception treatment. Levels of ETG and LNG in cervical secretions were 100–200 fold higher than plasma levels. In contrast, measurable MPA levels were approximately 10-fold higher in plasma compared to cervical secretions. These results will inform the design of accurate in vitro studies on the influence of progestins on epithelial cells, tissue explants, and peripheral blood cells, to be able to better predict in vivo outcomes. Subsequent observations will aid in determining how MPA might influence HIV acquisition and may facilitate identification of optimal progestin-containing LARC alternatives for women at high risk for HIV infection.

Resistance Profile of Neisseria gonorrhoeae in KwaZulu-Natal, South Africa Questioning the Effect of the Currently Advocated Dual Therapy.

We report on the antimicrobial resistance profile of Neisseria gonorrhoeae isolates and the distribution of tetM genes in isolates with high-level tetracycline resistance in KwaZulu-Natal, South Africa. Male and female patients presenting with urethral and/or vaginal discharge were recruited into the study. Urethral and cervical secretions were cultured on New York City agar. Confirmatory tests for N. gonorrhoeae included Gram stain, catalase, oxidase, and carbohydrate utilization tests. Beta-lactamase was tested by means of the chromogenic cephalosporin test. Minimum inhibitory concentrations were determined using agar dilution with multipoint inoculation. Polymerase chain reaction with gel electrophoresis was used to detect the presence and type of the tetM gene. N. gonorrhoeae was isolated from the specimens of 319 (26%) of the 1220 recruited patients. Of these 319 isolates, 71% were resistant to 3 or more drugs. Resistance to azithromycin was found in 68% of the isolates. All isolates showed high-level tetracycline resistance with minimum inhibitory concentration values of 16 and 32 mg/mL. The tetM gene was present in 293 (92%). The American type was found in 264 (90%) and the Dutch type in 29 (10%). Twenty-six (8%) did not carry a tetM gene. The current syndromic management with dual ceftriaxone and azithromycin is due to the high level of azithromycin resistance factually single-drug therapy. High-level tetracycline resistance based on a resistance mechanism other than ribosome protection by the tetM gene product is present in N. gonorrhoeae infecting South African patients.

Anti‐chlamydia IgG and IgA are insufficient to prevent endometrial chlamydia infection in women, and increased anti‐chlamydia IgG is associated with enhanced risk for incident infection

Chlamydia infections in women can ascend to the upper genital tract, and repeated infections are common, placing women at risk for sequelae. The protective role of anti-chlamydia antibodies to surface exposed antigens in ascending and incident infection is unclear. A whole-bacterial ELISA was used to quantify chlamydia-specific IgG and IgA in serum and cervical secretions of 151 high-risk women followed longitudinally. Correlations were determined between antibody and cervical burden, and causal mediation analysis investigated the effect of antibody on ascension. We examined the relationship of antibody to incident infection using the marginal Cox model. Serum and cervical anti-chlamydia IgG and cervical IgA levels correlated inversely with cervical burden. While lower burden was associated with reduced ascension, causal mediation analysis revealed that the indirect effects of antibody mediated through reductions in bacterial burden were insufficient to prevent ascension. Analysis of women uninfected at enrollment revealed that serum and cervical anti-chlamydia IgG were associated with increased risk of incident infection; hazard ratio increased 3.6-fold (95% CI, 1.3-10.3), and 22.6-fold (95% CI, 3.1-165.2) with each unit of serum and cervical IgG, respectively. Although anti-chlamydia IgG and IgA correlated with reduced cervical chlamydia burden, they failed to prevent ascension and increased levels of anti-chlamydia IgG were associated with increased risk for incident infection.

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection.

Chlamydia trachomatis can cause reproductive morbidities after ascending to the upper genital tract of women, and repeated infection can lead to worse disease. Data related to protective immune responses at the cervical mucosa that could limit chlamydial infection to the cervix and/or prevent reinfection inform vaccine approaches and biomarkers of risk. We measured 48 cytokines in cervical secretions from women having chlamydial cervical infection alone (n = 92) or both cervical and endometrial infection (n = 68). Univariable regression identified cytokines associated with differential odds of endometrial infection and reinfection risk, and multivariable stepwise regression identified cytokine ratios associated with differential risk. Elevated interleukin (IL) 15/CXCL10 (odds ratio [OR], 0.55 [95% confidence interval {CI}, .37-.78]), IL-16/tumor necrosis factor-α (OR, 0.66 [95% CI, .45-.93]), and CXCL14/IL-17A (OR, 0.73 [95% CI, .54-.97]) cytokine ratios were significantly (P ≤ .05) associated with decreased odds of endometrial infection. A higher Flt-3L/IL-14 ratio was significantly (P = .001) associated with a decreased risk of reinfection (hazard ratio, 0.71 [95% CI, .58-.88]). Cytokines involved in humoral, type I interferon, and T-helper (Th) 17 responses were associated with susceptibility to C. trachomatis, whereas cytokines involved in Th1 polarization, recruitment, and activation were associated with protection against ascension and reinfection.

A high concentration of fetal fibronectin in cervical secretions increases the risk of intra-amniotic infection and inflammation in patients with preterm labor and intact membranes

Objective To determine whether the risk of intra-amniotic infection/inflammation and spontaneous preterm delivery (SPTD) varies as a function of the concentration of cervical fetal fibronectin (fFN) in patients with preterm labor and intact membranes. Methods This prospective study included 180 patients with preterm labor and intact membranes who had a sample collected for quantitative fFN measurement and underwent amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Results (1) The prevalence of intra-amniotic infection/inflammation and SPTD within 7 days was 32.2% (58/180) and 33.9% (61/178), respectively; (2) The higher the fFN concentration, the greater the risk of intra-amniotic infection/inflammation and SPTD within 7 days (P<0.001, respectively); (3) An fFN concentration 150 ng/mL had a better diagnostic performance than an fFN 50 ng/mL in the identification of intra-amniotic infection/inflammation and SPTD within 7 days; (4) Among the patients with an fFN <50 ng/mL, intra-amniotic infection/inflammation was identified in 7.6% (6/79) of patients and 66.7% (4/6) delivered within 7 days. Conclusion The higher the concentration of fFN, the greater the risk of intra-amniotic infection/inflammation and SPTD in patients with preterm labor and intact membranes.

Detection of Chlamydia trachomatis Antigen in Cervical Secretions and Serum in Infertile Females Undergoing ICSI

Detection of Chlamydia trachomatis Antigen in Cervical Secretions and Serum in Infertile Females Undergoing ICSI

Follicular fluid composition of ovulatory follicles in repeat breeder Holstein dairy cows

Objective: To examine differences in the metabolite, steroid and lipopolysaccharide of follicular fluid collected from the ovulatory follicle of Holstein repeat breeding cows, lactating cows, and virgin fertile heifers. Methods: Estrus was induced in animals possessing functional corpus luteum by intramuscular administration of prostaglandin F2 α. Six to twelve hours after detection of the standing estrus, cervical samples were collected to detect subclinical endometritis via counting neutrophils on stained smears of cervical swabs. Then, follicular fluid of ovulatory follicles and serum samples were collected from repeat breeding cows (n=11), lactating cows (n=8) and virgin fertile heifers (n=10). Sodium and potassium were measured with a flame photometer method. Urea, total protein, glucose, cholesterol and β -hydroxybutyric acid were assayed with commercial spectrophotometry kits. Chloride concentration was also measured with titration of samples against silver nitrate. Progesterone, estradiol-17 β and lipopolysaccharide concentrations were measured using enzyme-linked immuno sorbent assay kits. Results: All analysis of follicular fluid samples showed that repeat breeding and lactating cows had a mean higher lipopolysaccharide concentration than that of the virgin fertile heifers (P Conclusions: High follicular fluid concentration of lipopolysaccharide in ovulatory follicles results in the occurrence of repeat breeding syndrome in dairy cows. Further, a lower serum estradiol-17 β concentration and a higher percentage of neutrophil in the cervical secretion on the day of artificial insemination may have resulted in the occurrence of repeat breeding syndrome in dairy cows.

How to Identify Exposed Women Who Are Infected with Neisseria gonorrhoeae.

Treatment trials of antibiotics for Neisseria gonorrhoeae infections frequently enroll primarily men with urethritis, as the diagnosis of acute gonococcal infection in men with urethritis is easily made by Gram stain of the urethral exudate, followed by confirmatory culture or nucleic acid amplification tests (NAATs). Enrolling women in treatment trials is of great importance, but N. gonorrhoeae cervical infections cause nonspecific symptoms. This makes it difficult to conduct interventional trials, as large numbers of women with nonspecific symptoms need to be screened for infection. Gram stain of cervical secretions has a strikingly low sensitivity, and culture and/or NAAT results are not available at the time of screening. This necessitates recall and delayed treatment of infected women who may not return and who may spread the infection during the interval. In this chapter we present an algorithm, derived from a comparison of women who did, or did not, become infected during exposure, which identifies those women who are highly likely to be infected before culture and/or NAAT results are available. The algorithm provides an efficient way to conduct interventional trials in women without the problem of recall and delayed treatment.

Low intensity laser effects on factors of congenital immunity and cytokine balance in secretions of female reproductive system affected with chlamydia infection

Therefore, we defined the objective of our research: to study the factors of uterine cervix tissue im- munity for women with Chlamydia infection and to estimate the effect of low-intensity laser therapy (LILT) on these factors due to a wavelength of 632 nm and a power of 30 mW. Materials and methods. Clinical immunologic studies of cervical secretion were carried out on 184 women of reproductive age 25,9 ± 4,22 in 2016–2018. Chlamydia infection Chlamydia trachomatis was found by the methods of real-time polymerase chain reaction (Rt-PCR) tests. Code by Classifier of the International Standard Classification of Diseases and Related Health Problems 10th Revision is А 56.0, Chlamydial infections of the lower sections of the urogenital tract. Urethra and canalis cervicis uteri scrapings were used as the material for detecting C. trachomatis. All patients with chlamydial infection of the lower part of the urogenital system were divided into two groups: a group of 100 women who were treated by using the local influence of the low-intensity laser of 632 nm as a part of complex treatment, the comparison group (basic treatment) consisted of 84 women who took azithromycin of 1 g once a day for the 1st, 5th, 10th days of treatment. 50 healthy women without any pathology and infections of the genitourinary system made the control group. A system of cytokines was studied by interleukin's level IL-8. IL-1 α, IL-1 β, TNF-α and IFN-γ content in cervical mucus. Results Course. The results of the study showed a high clinical and immunological efficacy of treating chlamydial cervicitis using a low intensity laser with a wavelength of 632 nm. An imbalance of cellular factors of innate immunity revealed before starting a therapy: a decrease in the oxygen-dependent metabolism of neutrophilic granulocytes of the cervical secretion.

Time Intervals Between Prior Cervical Conization and Posterior Hysterectomy Influence Postoperative Infection in Patients with Cervical Intraepithelial Neoplasia or Cancer.

BackgroundThis study was conducted to observe the influence of different time intervals between prior cervical conization and posterior hysterectomy on postoperative infection in female patients with cervical intraepithelial neoplasia or cancer.Material/MethodsMedical records of 170 patients who underwent hysterectomy following cervical conization between November 2010 and September 2016 at the Zhenjiang 4th Hospital were reviewed. According to the interval between hysterectomy and cervical conization, patients were classified into 1–2-week, 4–5-week, and 6-week groups. The outcomes of 46 patients who underwent conization with iodoform gauze inside the vagina were observed.ResultsThe total postoperative infection rate after hysterectomy was 25.3% (43/170). The expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1) in the cervical secretions and tissues were found to gradually increase, peaking at 2 weeks after conization, then significantly decreasing 3–6 weeks onwards. Compared with the 1–2-week group, the 4–5-week and 6-week groups exhibited significantly lower infection rates (2/42, 4.8%, 4–5-week group; 0%, 0/33, 6-week group; vs. 41/95, 43.2%, 1–2-week group; p<0.001). In the 1–2-week group in particular, the postoperative infection rate after laparoscopic hysterectomy was significantly higher than the rate after abdominal hysterectomy (21/35, 60% vs. 20/60, 33%, p=0.0177). In addition, the vaginal and cervical wound infection rates after conization in patients treated with iodoform were significantly lower than the rates in those without iodoform treatment (p<0.05).ConclusionsHysterectomy should be performed at least 4 weeks after conization. Treatment with iodoform would be beneficial.

Potential Biomarkers for Predicting Congenital Cytomegalovirus Infection

Early diagnosis and treatment of infants with symptomatic congenital cytomegalovirus (CMV) infection may improve neurological outcomes. For this reason, prenatal detection of newborns at high risk for congenital CMV infection is important. A polymerase chain reaction (PCR) assay for CMV DNA in the amniotic fluid is the gold standard for the diagnosis of intrauterine CMV infection; however, amniocentesis is an invasive procedure. Recently, we have found that the presence of CMV DNA in the maternal uterine cervical secretion is predictive of the occurrence of congenital CMV infection in CMV immunoglobulin M (IgM)-positive pregnant women. In contrast, we have suggested that maternal serological screening for primary CMV infection using CMV-specific immunoglobulin G (IgG), the IgG avidity index, or CMV-specific IgM overlooks a number of newborns with congenital CMV infection. We will review current knowledge of the potential biomarkers for predicting congenital CMV infection.

Predictors, Treatment and Prevention of Preterm Labour: A Review

Preterm labour (PTL) is one of the leading causes of neonatal morbidity and mortality throughout the world. It is also a major public health problem for its long-term disabilities like cerebral palsy and visual disturbance. Preterm labour is a multifactorial problem and its overall global incidence is 11.1 per 100 live births with a significant regional variation. About 45-50% of preterm deliveries are spontaneous, 30% are associated with preterm prelabour rupture of membranes (PPROM) and another 15-25% is induced for maternal and/or foetal risk. Previous history of PTL is an important risk factor; risk is 14.3% after one preterm birth and 28% after two preterm births. Other important risk factors are multiple pregnancy, polyhydramnios, bicornuate uterus, cervical incompetence &amp; bacterial vaginosis. Prediction of PTL is very difficult but identification of risk factors, assessment of cervical length by ultrasonography and detection of foetal fibronectin in cervical secretions are of great help. Advanced cervical dilatation (&gt;3 cm) or PPROM associated with sufficient and frequent uterine contractions confirm the diagnosis of preterm labour. Prevention of PTL has been tried with prophylactic cervical cerclage, antibiotics and progesterone. PTL is treated with various tocolytic agents and glucucorticoids and antibiotics for local or systemic infection. Betamimetics, calcium channel blockers (nifedipine), prostaglandin synthesis inhibitors and magnesium sulfate are the commonly used tocolytics. Nifedipine has significantly fewer maternal adverse effects than betamimetics and magnesium sulphate. Antenatal corticosteroid treatment has been found to lower neonatal mortality, the risk of neonatal respiratory distress syndrome, intraventricular hemorrhage and necrotizing enterocolitis. The ultimate goal of prevention and management of preterm labour is to improve neonatal outcome and to reduce morbidity and mortality.Journal of Science Foundation, July 2017;15(2):57-63

Fetal Fibronectin Test Performance in Patients at Low Risk for Preterm Delivery

Objectives: Spontaneous preterm birth is a leading cause of neonatal death. Fetal fibronectin (fFN) testing in cervical secretions between 22-34.6 weeks of gestation is used to predict non-delivery within the next 7 days in patients with symptoms of preterm labor. The objective of this study is to analyze fFN test performance in a group of patients with low risk for preterm delivery that presented with preterm labor symptoms, and to evaluate how the results of fFN testing influenced management decisions. Materials and Methods: Patients after preterm delivery (gestational age 24.0-36.6 weeks) and patients who underwent fFN testing in Metropolitan Hospital, NYC Health+Hospitals, New York, NY, from January 1, 2015 to December 31, 2015 were identified and reviewed. Patients with positive fFN test results (fFN+; &gt;50 ng/dL) were compared to patients with negative fFN test results (fFN-). Results: Among 77 patients identified, 66 (86%) were fFN- and 11 (14%) fFN+; 15 patients (78%) who delivered preterm were not tested with fFN. Preterm birth rate during the study period was 1.9%. There was no difference in maternal or neonatal characteristics between the two groups. Among fFN-, 4 patients (6%) delivered preterm, while among fFN+, none delivered preterm. In both groups, none delivered within 7 days of testing. Compared to fFN-, fFN+ had higher rates of admissions (36% vs 0%; P&lt;0.001) and steroid administration (82% vs 0%; P&lt;0.001). Conclusions: In this retrospective analysis, use of fFN testing as an initial screening test for patients with symptoms of preterm labor in this low risk population did not result in improved clinical outcomes and was associated with a higher rates of hospital admissions and steroid administration.

PREVENTION OF PREMATURE LABOR IN PREGNANT WOMEN WITH PREVIOUS PREVENTION

Introduction.The problem of preterm labor is always relevant component of all complications of pregnancy. One of the most promising methods for predicting preterm labor is, at present, the detection of fetal fibronectin (fFN) and the determination of the content of interleukins in the blood or cervical secretions, in particular, the importance of interleukin 8 (IL-8).Aim. Determine the efficiency of prediction of preterm labor by simultaneously identifying fFN and IL-8 as markers of probable preterm labor.Materials and methods. Clinical and laboratory examination of 60 pregnant women was carried out: 40 - the main group with false contractions up to 37 weeks; 20 - control group, pregnant without this pathology. Definition of fFN andIL-8 was performed simultaneously in blood serum and cervical mucus with the evaluation of the results on the Rider Myltiskan EX immuno-enzyme analyzer using a set of reagents and test systems.Research results. An analysis of the effectiveness of diagnosis of preterm labor in pregnant women with false contractions up to 37 weeks using transvaginal cervicomercia revealed a shortening of the cervix in terms of 22-27 weeks in 5% and in 31-33 weeks in 10% and changes from the FF values in terms of 22- 27 weeks and 28-33 weeks - where its level was elevated both in serum and in cervical mucus and was 331.5 ± 40.4 and 1510 ± 17.9 respectively; 349.3 ± 45.2 and 128.6 ± 22.7 ng / ml. The probable correlation between increased fetal fibronectin and structural changes in the cervix was established (the correlation coefficient of the reciprocal connection was R = 0.50). Taking into account the data of urogenital stroke and the content of IL-8 in cervical mucus, it was found that an increase in the number of leukocytes, indicating inflammation, and an increase in IL-8 in 47.8% during the period of pregnancy 22-27 weeks + 6 days and in the 31- 33 weeks + 6 days in 55.6%, where the mean IL-8 was 132.5 ng / ml and 33.3% of the background cervical cancer.Conclusions. In the presence of false breaks and premature births, regardless of the period of pregnancy, there is a significant increase in IL-8. The probable correlation between increased fetal fibronectin in blood serum and in cervical mucus and structural changes in the cervix (correlation coefficient of mutual communication was R = 0.50) was established.

Interferon epsilon in the reproductive tract of healthy and genital herpes simplex virus-infected pregnant women: Results of a pilot study.

Recently characterized interferon epsilon (IFNe) protects against sexually transmitted infections, including genital herpes simplex virus (HSV), in animal models. There are no reports of IFNe in genital tract secretions of pregnant women, and data on IFNe in non-pregnant women are limited. This pilot study is the first to measure concentrations of IFNe in vaginal and cervical secretions during pregnancy and compare values between healthy and genital HSV-infected women. Vaginal or cervical specimens from 30 pregnant women were obtained from the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) repository. Cervical samples were collected during the first trimester and vaginal samples across pregnancy. Enzyme-linked immunosorbent assay determined concentrations of IFNe (pg/mL). Data for IFNe were log-transformed and compared by maternal demographics, clinical variables, and HSV status using t tests and linear regression. Repeated measures analysis explored trends across pregnancy. Among the entire cohort, first trimester concentrations of IFNe in vaginal or cervical secretions decreased as body mass index increased (β=-0.14, P=.0466). Concentrations of vaginal IFNe increased across pregnancy in HSV-infected and healthy women (P=.009). Average vaginal IFNe across pregnancy was lower in women with HSV compared to healthy women (P=.0009). Interferon epsilon increased across pregnancy, but was less abundant in women with HSV. This pilot investigation cannot make any definitive conclusions. However, animal models suggest that IFNe may protect against STIs. Thus, larger studies are required to validate expression of IFNe in the reproductive tract of pregnant women with and without genital infections.

Chlamydia trachomatis-infected cells and uninfected-bystander cells exhibit diametrically opposed responses to interferon gamma

The intracellular bacterial pathogen, Chlamydia trachomatis, is a tryptophan auxotroph. Therefore, induction of the host tryptophan catabolizing enzyme, indoleamine-2,3-dioxgenase-1 (IDO1), by interferon gamma (IFNγ) is one of the primary protective responses against chlamydial infection. However, despite the presence of a robust IFNγ response, active and replicating C. trachomatis can be detected in cervical secretions of women. We hypothesized that a primary C. trachomatis infection may evade the IFNγ response, and that the protective effect of this cytokine results from its activation of tryptophan catabolism in bystander cells. To test this hypothesis, we developed a novel method to separate a pool of cells exposed to C. trachomatis into pure populations of live infected and bystander cells and applied this technique to distinguish between the effects of IFNγ on infected and bystander cells. Our findings revealed that the protective induction of IDO1 is suppressed specifically within primary infected cells because Chlamydia attenuates the nuclear import of activated STAT1 following IFNγ exposure, without affecting STAT1 levels or phosphorylation. Critically, the IFNγ-mediated induction of IDO1 activity is unhindered in bystander cells. Therefore, the IDO1-mediated tryptophan catabolism is functional in these cells, transforming these bystander cells into inhospitable hosts for a secondary C. trachomatis infection.

Depo-Provera alters cervical immune responses and increases HIV infectivity ex vivo: a longitudinal study.

Abstract Depo-Provera (Depot medroxyprogesterone acetate, MPA) is associated with an increased risk of HIV acquisition; however, its impact on the cervicovaginal immune milieu and HIV infectivity ex vivo is not well characterized. In a longitudinal study, we investigated the impact of Depo-Provera use by healthy women on levels of cervical immune mediators, expression of immune markers for HIV preference (CCR5, integrin a4b7, CD38) on cervical CD4+ T cells, and HIV infectivity ex vivo at baseline (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment. Forty-seven healthy women who met the eligibility criteria were enrolled (median age 26, IQR 22.5–30). Cervical cytobrush cells and secretions from vaginal, endocervical, and rectal swabs were collected. Flow cytometry analysis indicated a significant increase in the frequency of cervical CCR5+CD4+T cells at visit 3 compared to visit 1. There was also an increasing trend in the frequency of cervical CD4+ cells expressing integrin a4b7 in response to Depo-Provera. Levels of several cytokines including G-CSF, GM-CSF, IL-6, MIP-1b, and VEGF in vaginal and cervical secretions were significantly decreased at visits 2 and 3 compared to visit 1. At visit 3, cervical levels of immune mediators remained suppressed despite a decreased serum concentration of MPA, suggesting a prolonged effect of Depo-Provera on mucosal immune responses. Cervicovaginal secretions from women after receiving Depo-Provera (visits 2 and 3) promoted HIV infectivity ex vivo compared to those at visit 1. Further studies on the modulation of mucosal immune responses and HIV transmission by Depo-Provera will offer insights into developing better strategies for HIV prevention.