IL-17C is a driver of damaging inflammation during Neisseria gonorrhoeae infection of human Fallopian tube.

The human pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within the Fallopian tubes and pelvic inflammatory disease (PID), increasing the risk of infertility and ectopic pregnancy. The loss of ciliated cells from the epithelium is thought to be both a consequence of inflammation and a cause of adverse sequelae. However, the links between infection, inflammation, and ciliated cell extrusion remain unresolved. With the use of ex vivo cultures of human Fallopian tube paired with RNA sequencing we defined the tissue response to gonococcal challenge, identifying cytokine, chemokine, cell adhesion, and apoptosis related transcripts not previously recognized as potentiators of gonococcal PID. Unexpectedly, IL-17C was one of the most highly induced genes. Yet, this cytokine has no previous association with gonococcal infection nor pelvic inflammatory disease and thus it was selected for further characterization. We show that human Fallopian tubes express the IL-17C receptor on the epithelial surface and that treatment with purified IL-17C induces pro-inflammatory cytokine secretion in addition to sloughing of the epithelium and generalized tissue damage. These results demonstrate a previously unrecognized but critical role of IL-17C in the damaging inflammation induced by gonococci in a human explant model of PID.

Elevated peritoneal soluble endoglin and GDF-15 in infertile women with severe endometriosis and pelvic adhesion.

OBJECTIVES: Chronic inflammation and pelvic adhesion play a critical role in endometriosis-related infertility. Research studies suggest that TGF-ß superfamily members, such as soluble endoglin (sEng), growth differentiation factor 15 (GDF-15) and tumor growth factor-beta (TGF-ß1) contribute to the regulation of inflammation, angiogenesis and cell adhesion. The objective of this study is to investigate the association between the concentrations of these TGF-ß-related members and the clinical parameters of infertile women with endometriosis. MATERIALS AND METHODS: Sixty-five infertile women who underwent laparoscopy were divided into two groups in this study: those who had endometriosis (n = 33) and control subjects with benign gynecologic disorders (n = 32). The levels of TGF-ß- related members in peritoneal fluid and serum were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. RESULTS: Endometriosis cases had significantly higher levels of sEng, GDF-15 and TGF-ß1 in peritoneal fluid (p<0.0005) compared to control subjects, but not in serum. Moreover, serum GDF-15 level was significantly elevated in the late-stage endometriosis compared to the early-stage group. The levels of three TGF-ß related molecules in peritoneal fluid showed positive correlations with rASRM score. Blood neutrophil counts have correlation with the peritoneal sEng concentration. CONCLUSION: Our novel evidence on the elevated concentration of peritoneal sEng and GDF-15 in endometriosis, specifically in the late-stage, may indicate the essential role of TGF-ß-dependent signaling in endometriosis. Serum GDF-15 might serve as a candidate biomarker for endometriosis severity. Further studies are warranted to investigate the role and regulation of these molecules in endometriosis.

Aldose Reductase Inhibitor Engeletin Suppresses Pelvic Inflammatory Disease by Blocking the Phospholipase C/Protein Kinase C-Dependent/NF-κB and MAPK Cascades.

Pelvic inflammatory disease (PID) is a common inflammation in the upper reproductive tract in women and may cause serious and costly consequences without effective treatment. Engeletin is a flavanonol glycoside and a naturally derived aldose reductase (AR) inhibitor that is widely distributed in vegetables, fruits, and plant-based foods. The present study investigated the anti-PID activity of engeletin in a mucilage-induced rat model of PID and LPS-stimulated RAW 264.7 macrophages. Engeletin significantly reduced inflammation and ameliorated the typical uterine pathological changes in PID rats. Engeletin also inhibited AR-dependent PLC/PKC/NF-κB and MAPK inflammatory pathways, as indicated by the suppression of the phosphorylation levels of PLC, PKC, p38, ERK, and JNK and the nuclear translocation of NF-κB p65. In vitro studies demonstrated that engeletin significantly inhibited inflammatory mediator expression and enhanced the phagocytic ability of LPS-induced RAW 264.7 macrophages. RNA interference of AR prevented the engeletin-induced inhibition of inflammatory mediators. Engeletin also inhibited AR-dependent PLC/PKC/NF-κB and MAPK inflammatory pathways, which was consistent with the in vivo results. These findings support engeletin as a potential agent for prevention or treatment of PID.

[Determination of antispermal IgE antibodies in women with infertility and chronic inflammatory pelvic diseases.] / Определение Ð°Ð½Ñ‚Ð¸ÑÐ¿ÐµÑ€Ð¼Ð°Ð»ÑŒÐ½Ñ‹Ñ IgE антител у женщин с бесплодием, ÑÑ‚Ñ€Ð°Ð´Ð°ÑŽÑ‰Ð¸Ñ Ñ Ñ€Ð¾Ð½Ð¸Ñ‡ÐµÑÐºÐ¸Ð¼Ð¸ воспалительными заболеваниями органов малого таза.

Personalized therapy for female infertility means determining of immune mechanisms, including allergic sensitization towards sperm antigens. In order to determine antisperm serum IgE antibodies in women with infertility suffering from pelvic inflammatory diseases, the modified Anti-Spermatozoa Antibody protocol was used (ASA Serum ELISA, Demeditec Diagnostisc, Germany). The modification of the protocol is designed to detect only serum antisperm IgE antibodies carrying Fab fragments to sperm antigens. Allergen-specific IgEs to a common panel of 176 respiratory and food allergenic molecules were determined using the MeDALL scientific chip developed as a part of the European project. Forty patients suffering from infertility of inflammatory etiology and 16 practically healthy women of reproductive age were examined. Specific IgE antibodies towards sperm antigens were detected in blood serum in 7/40 (17.5%) patients with infertility. The maximum level of sIgE was 4 times higher than the maximal value of fertile women. No correlation with total IgE was detected. Women with sIgE-ASA complained of burning and itching immediately after coition. Systemic and long-term allergic reactions were not noted. Women with positive sIgE-ASA values were 2 times more likely to suffer from chronic recurrent vaginal dysbiosis. The presence of specific anti-sperm IgE antibodies is likely to have pathogenetic significance in female infertility, and they should be taken into consideration for creating personalized therapy approaches.

Chlamydia trachomatis and the Risk of Pelvic Inflammatory Disease, Ectopic Pregnancy, and Female Infertility: A Retrospective Cohort Study Among Primary Care Patients.

BACKGROUND: We evaluated the risk of pelvic inflammatory disease (PID), ectopic pregnancy, and infertility in women with a previous Chlamydia trachomatis (CT) diagnosis compared with women who tested negative for CT and CT untested women, considering both targeted and incidental (ie, prescribed for another indication) use of CT-effective antibiotics. METHODS: This was a retrospective study of women aged 12-25 years at start of follow-up within the Clinical Practice Research Datalink GOLD database linked to index of multiple deprivation quintiles, 2000-2013. CT test status and antibiotic use were determined in a time-dependent manner. Risk of PID, ectopic pregnancy, or female infertility were evaluated using of Cox proportional hazard models. RESULTS: We studied 857 324 women, contributing 6 457 060 person-years. Compared with women who tested CT-negative, women who tested CT-positive had an increased risk of PID (adjusted hazard ratio [aHR], 2.36; 95% confidence interval [CI], 2.01-2.79), ectopic pregnancy (aHR, 1.87; 95% CI, 1.38-2.54), and infertility (aHR, 1.85; 95% CI, 1.27-2.68). The PID risk was higher for women with 2 or more positive CT tests than those with 1 positive test. PID risk increased with the number of previous antibiotic prescriptions, regardless of CT test status. CONCLUSIONS: We showed an association between CT-positive tests and 3 adverse reproductive health outcomes. Moreover, this risk increased with repeat CT infections. CT-effective antibiotic use showed no decreased risks of subsequent PID regardless of CT history. Our results confirm the reproductive health burden of CT, which requires adequate public health interventions.

Effect of Time of Day of Infection on Chlamydia Infectivity and Pathogenesis.

Genital chlamydia infection in women causes complications such as pelvic inflammatory disease and tubal factor infertility, but it is unclear why some women are more susceptible than others. Possible factors, such as time of day of chlamydia infection on chlamydial pathogenesis has not been determined. We hypothesised that infections during the day, will cause increased complications compared to infections at night. Mice placed under normal 12:12 light: dark (LD) cycle were infected intravaginally with Chlamydia muridarum either at zeitgeber time 3, ZT3 and ZT15. Infectivity was monitored by periodic vaginal swabs and chlamydiae isolation. Blood and vaginal washes were collected for host immunologic response assessments. The reproductive tracts of the mice were examined histopathologically, and fertility was determined by embryo enumeration after mating. Mice infected at ZT3 shed significantly more C. muridarum than mice infected at ZT15. This correlated with the increased genital tract pathology observed in mice infected at ZT3. Mice infected at ZT3 were less fertile than mice infected at ZT15. The results suggest that the time of day of infection influences chlamydial pathogenesis, it indicates a possible association between complications from chlamydia infection and host circadian clock, which may lead to a better understanding of chlamydial pathogenesis.

Biological feasibility and importance of a gonorrhea vaccine for global public health.

There is a growing public health interest in controlling sexually transmitted infections (STIs) through vaccination due to increasing recognition of the global disease burden of STIs and the role of STIs in women's reproductive health, adverse pregnancy outcomes, and the health and well-being of neonates. Neisseria gonorrhoeae has historically challenged vaccine development through the expression of phase and antigenically variable surface molecules and its capacity to cause repeated infections without inducing protective immunity. An estimated 78 million new N. gonorrhoeae infections occur annually and the greatest disease burden is carried by low- and middle-income countries (LMIC). Current control measures are clearly inadequate and threatened by the rapid emergence of antibiotic resistance. The gonococcus now holds the status of "super-bug" as there is currently no single reliable monotherapy for empirical treatment of gonorrhea. The problem of antibiotic resistance has elevated treatment costs and necessitated the establishment of large surveillance programs to track the spread of resistant strains. Here we review the need for a gonorrhea vaccine with respect to global disease burden and related socioeconomic and treatment costs, with an emphasis on the impact of gonorrhea on women and newborns. We also highlight the challenge of estimating the impact of a gonorrhea vaccine due to the need for more data on the burden of gonococcal pelvic inflammatory disease and related sequelae and of gonorrhea-associated adverse pregnancy outcomes and the problem of empirical diagnosis and treatment of STIs in LMIC. There is also a lack of clinical and basic science research in the area of gonococcal/chlamydia coinfection, which occurs in a high percentage of individuals with gonorrhea and should be considered when testing the efficacy of gonorrhea vaccines. Finally, we review recent research that suggests a gonorrhea vaccine is feasible and discuss challenges and research gaps in gonorrhea vaccine development.

Pathogenesis of Neisseria gonorrhoeae and the Host Defense in Ascending Infections of Human Fallopian Tube.

Neisseria gonorrhoeae is an obligate human pathogen that causes mucosal surface infections of male and female reproductive tracts, pharynx, rectum, and conjunctiva. Asymptomatic or unnoticed infections in the lower reproductive tract of women can lead to serious, long-term consequences if these infections ascend into the fallopian tube. The damage caused by gonococcal infection and the subsequent inflammatory response produce the condition known as pelvic inflammatory disease (PID). Infection can lead to tubal scarring, occlusion of the oviduct, and loss of critical ciliated cells. Consequences of the damage sustained on the fallopian tube epithelium include increased risk of ectopic pregnancy and tubal-factor infertility. Additionally, the resolution of infection can produce new adhesions between internal tissues, which can tear and reform, producing chronic pelvic pain. As a bacterium adapted to life in a human host, the gonococcus presents a challenge to the development of model systems for probing host-microbe interactions. Advances in small-animal models have yielded previously unattainable data on systemic immune responses, but the specificity of N. gonorrhoeae for many known (and unknown) host targets remains a constant hurdle. Infections of human volunteers are possible, though they present ethical and logistical challenges, and are necessarily limited to males due to the risk of severe complications in women. It is routine, however, that normal, healthy fallopian tubes are removed in the course of different gynecological surgeries (namely hysterectomy), making the very tissue most consequentially damaged during ascending gonococcal infection available for laboratory research. The study of fallopian tube organ cultures has allowed the opportunity to observe gonococcal biology and immune responses in a complex, multi-layered tissue from a natural host. Forty-five years since the first published example of human fallopian tube being infected ex vivo with N. gonorrhoeae, we review what modeling infections in human tissue explants has taught us about the gonococcus, what we have learned about the defenses mounted by the human host in the upper female reproductive tract, what other fields have taught us about ciliated and non-ciliated cell development, and ultimately offer suggestions regarding the next generation of model systems to help expand our ability to study gonococcal pathogenesis.

Discovery of Blood Transcriptional Endotypes in Women with Pelvic Inflammatory Disease.

Sexually transmitted infections with Chlamydia trachomatis and/or Neisseria gonorrhoeae and rates of pelvic inflammatory disease (PID) in women continue to rise, with reinfection being common because of poor adaptive immunity. Diagnosis remains imprecise, and pathogenesis data are derived primarily from monoinfection of mice with C. trachomatis or N. gonorrhoeae By comparing blood mRNA responses of women with C. trachomatis- and/or N. gonorrhoeae-induced PID and histologic endometritis with those from women with C. trachomatis and/or N. gonorrhoeae infection limited to their cervix and asymptomatic uninfected women determined via microarray, we discovered important pathogenic mechanisms in PID and response differences that provide a pathway to biomarker discovery. Women with N. gonorrhoeae- and/or C. trachomatis-induced PID exhibit overexpression of myeloid cell genes and suppression of protein synthesis, mitochondrial oxidative phosphorylation, and T cell-specific genes. Coinfected women exhibited the greatest activation of cell death pathways and suppression of responses essential for adaptive immunity. Women solely infected with C. trachomatis expressed elevated levels of type I and type II IFN genes, and enhanced type I IFN-induced chemokines in cervical secretions were associated with ascension of C. trachomatis to the endometrium. Blood microarrays reveal discrete pathobiological endotypes in women with PID that are driven by pathogen invasion of the upper genital tract.

The reproductive cycle is a pathogenic determinant during gonococcal pelvic inflammatory disease in mice.

Women with asymptomatic Neisseria gonorrhoeae infection are at risk of developing pelvic inflammatory disease (PID) if the bacteria ascend from the endocervix into the uterus and oviducts. Factors that affect disease severity, ranging from mild discomfort to severe inflammation, pain, and infertility, remain elusive. Herein we perform direct transcervical inoculation of N. gonorrhoeae into the uterus of mice to establish an infection that leads to PID. Profoundly different disease outcomes were apparent at different stages of the reproductive cycle. Mice that were infected during the diestrus stage of the reproductive cycle displayed extensive gonococcal penetration into the submucosa, severe inflammation, and clinical signs reflecting discomfort. Meanwhile, infection during the intervening estrus stage showed only modest effects. Furthermore, a gonococcal-specific humoral response was only elicited following the penetrative upper genital tract (UGT) infection during diestrus but not estrus. Strikingly, the potential for antibodies to contribute to protection during re-infection also depends upon the reproductive stage, as antigonococcal antibodies within the genital tract were markedly higher when mice were in diestrus. Combined, this work establishes a robust new model reflecting gonococcal PID in humans and reveals how the reproductive cycle determines the pathogenic outcome of gonococcal infections of the UGT.

Hyperketonemia in early lactation dairy cattle: a deterministic estimate of component and total cost per case.

The purpose of this study was to develop a deterministic economic model to estimate the costs associated with (1) the component cost per case of hyperketonemia (HYK) and (2) the total cost per case of HYK when accounting for costs related to HYK-attributed diseases. Data from current literature was used to model the incidence and risks of HYK (defined as a blood ß-hydroxybutyrate concentration≥1.2 mmol/L), displaced abomasa (DA), metritis, disease associations, milk production, culling, and reproductive outcomes. The component cost of HYK was estimated based on 1,000 calvings per year; the incidence of HYK in primiparous and multiparous animals; the percent of animals receiving clinical treatment; the direct costs of diagnostics, therapeutics, labor, and death loss; and the indirect costs of future milk production losses, future culling losses, and reproduction losses. Costs attributable to DA and metritis were estimated based on the incidence of each disease in the first 30 DIM; the number of cases of each disease attributable to HYK; the direct costs of diagnostics, therapeutics, discarded milk during treatment and the withdrawal period, veterinary service (DA only), and death loss; and the indirect costs of future milk production losses, future culling losses, and reproduction losses. The component cost per case of HYK was estimated at $134 and $111 for primiparous and multiparous animals, respectively; the average component cost per case of HYK was estimated to be $117. Thirty-four percent of the component cost of HYK was due to future reproductive losses, 26% to death loss, 26% to future milk production losses, 8% to future culling losses, 3% to therapeutics, 2% to labor, and 1% to diagnostics. The total cost per case of HYK was estimated at $375 and $256 for primiparous and multiparous animals, respectively; the average total cost per case of HYK was $289. Forty-one percent of the total cost of HYK was due to the component cost of HYK, 33% to costs attributable to metritis, and 26% to costs attributable to DA. The high total cost of HYK at reported incidences of 40 to 60% highlights the importance of appropriate transition cow nutrition and management to decrease the effect of HYK.

Gardnerella vaginalis triggers NLRP3 inflammasome recruitment in THP-1 monocytes.

Gardnerella vaginalis is a Gram-positive bacterium associated with bacterial vaginosis (BV), pelvic inflammatory disease, and preterm birth. BV is the most prevalent vaginal dysbiosis in women of childbearing age characterized by the absence of normal lactobacilli and an overgrowth of G. vaginalis and other bacteria. Although mucosal fluids from BV patients exhibit increases in proinflammatory cytokines and Toll-like receptor 2 and 4 mRNA, G. vaginalis has not been demonstrated to directly induce an inflammatory response. This study tested the hypothesis that G. vaginalis induces an inflammatory response in the human monocyte cell line, THP-1. The objectives of the study were to measure proinflammatory cytokine production, molecular mechanisms by which cytokines are produced, and whether G. vaginalis results in death of the monocytic cells. We found that G. vaginalis induced significant increases in the inflammasome-dependent cytokines IL-1ß, IL-18, as well as TNF-α in treated cells. G. vaginalis caused significant cell death by 24h post-treatment compared with untreated controls, but cells remained 66% viable. Caspase-1 cleavage in treated cells confirmed the inflammatory cell death, and NLRP3 knockdown confirmed its involvement through reduction of IL-1ß secretion. Using a stably expressing YFP-ASC THP-1 cell model with immunofluorescent staining, YFP-ASC colocalized with NLRP3 in G. vaginalis-treated cells and the addition of a caspase-1 inhibitor wholly ameliorated IL-1ß secretion. Our study provides new insight into the role of G. vaginalis in inflammatory conditions in the genital tract.

[Expression of TLR2 and TLR9 genes by epithelial cells of cervical canal mucous membrane in women with inflammatory diseases of small pelvis organs].

AIM: Determine subpopulation composition of blood lymphocytes and the level of expression of TLR2 and TLR9 by epithelial cells of cervical canal mucous membrane in women of reproductive age with inflammatory disease of small pelvis organs (IDSPO) at exacerbation stage and remission period. MATERIALS AND METHODS: Clinical-laboratory and gynecological examination of 105 women was carried out and 3 groups were formed based on the results: patients at IDSPO exacerbation stage; patients at remission stage; clinically healthy women. By using real time PCR, TLR2, TLR9 gene expression levels were determined in epithelial cells of cervical canal mucous membrane in women of all the 3 groups. Subpopulation composition of blood lymphocytes was determined by flow cytofluorimetry by using monoclonal antibodies with CD45+ CD3+ -T-cell, CD45+ CD3+ CD4+ -T-helper, CD45+, CD3+, CD8+ -T-suppressors-cytotoxic killers, CD45+, CD3-, CD16+, CD56+ natural killers, CD45+, CD3-, CD19+ -B-lymphocytes. Immune fluorescence reaction evaluation was carried out in flow cytofluorimeter Cytomics FC 500 (Becton Coulter, USA). RESULTS: The level of expression of TLR2 gene in the studied groups of patients was established not to differ significantly from parameters in the comparison groups, however it should be noted that this parameter in women with IDSPO at exacerbation stage (causative agents of the infectious process--ureaplasma, staphylococcus, candida) was somewhat higher than in the comparison group. Significantly high level of TLR9 gene expression in cervical canal epithelial cells was detected to correlate with the presence of infectious causative agents. In the group of women with exacerbation of the infectious process the expression of TLR9 was 14.5 times higher compared with the group of women without IDSPO. Among groups of women with IDSPO significant differences in relation to control group in relative and absolute levels of CD3+ T-lymphocytes; CD4+ T-helpers; CD8+ cytotoxic killer T-suppressors, B-lymphocytes compared with the same parameters in clinically healthy women were not detected. CONCLUSION: The increase of TLR9 gene expression level in cervical canal cells of women with IDSPO may serve as an additional diagnostic feature of the presence and degree of severity of the disease.

[Detection of the interferon deficiency in inflammatory gynecological diseases and its correction with interferon inducers].

Interferons deficiency has a negative influence on the development of infection and inflammation in general. The use in the complex of anti-inflammatory therapy of interferon inducers (Meglumine acridоnacetate, Tilorone), combining antiviral, immunomodulatory, interferon correction effects with etiopathogenic action leads to the correction of the interferon system defects and eliminate etiological infectious agents, that is confirmed by laboratory data and clinical efficacy.

[The investigation of prevalence of genital inflammation in women of second generation of descendants whose ancestors were in the area of radiation exposure].

There are the results of a comprehensive clinical examination of 112 women of childbearing age who are second generation descendants of those who were in the area of radiation exposure over 25 ED cSv. Incidence and factors leading to chronic inflammation of pelvic organs were studied. Immune status was evaluated by studying of subpopulation of immune cells in peripheral blood and levels of basic inflammatory cytokines. High incidence of the pelvic organs inflammatory diseases in women second-generation offspring due to disturbances in the complex chain of immunocompetent system was defined.

Persistent Mycoplasma genitalium infection of human endocervical epithelial cells elicits chronic inflammatory cytokine secretion.

Infection with Mycoplasma genitalium has been associated with male and female urogenital disease syndromes, including urethritis, cervicitis, pelvic inflammatory disease (PID), and tubal factor infertility. Basic investigations of mucosal cytotoxicity, microbial persistence, and host immune responses are imperative to understanding these inflammatory urogenital syndromes, particularly in females, considering the potential severity of upper tract infections. Here, we report that M. genitalium can establish long-term infection of human endocervical epithelial cells that results in chronic inflammatory cytokine secretion and increased responsiveness to secondary Toll-like receptor (TLR) stimulation. Using a novel quantitative PCR assay, M. genitalium was shown to replicate from 0 to 80 days postinoculation (p.i.), during which at most time points the median ratio of M. genitalium organisms to host cells was ≤10, indicating that low organism burdens are capable of eliciting chronic inflammation in endocervical epithelial cells. This observation is consistent with clinical findings in women. Persistently secreted cytokines predominately consisted of potent chemotactic and/or activating factors for phagocytes, including interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1ß (MIP-1ß). Despite persistent cytokine elaboration, no host cell cytotoxicity was observed except with superphysiologic loads of M. genitalium, suggesting that persistent infection occurs with minimal direct damage to the epithelium. However, it is hypothesized that chronic chemokine secretion with leukocyte trafficking to the epithelium could lead to significant inflammatory sequelae. Therefore, persistent M. genitalium infection could have important consequences for acquisition and/or pathogenesis of other sexually transmitted infections (STIs) and perhaps explain the positive associations between this organism and human immunodeficiency virus (HIV) shedding.

Variants in toll-like receptor 1 and 4 genes are associated with Chlamydia trachomatis among women with pelvic inflammatory disease.

BACKGROUND: Toll-like receptors (TLRs) are involved in the innate immune response. We examined whether TLR variants are associated with Chlamydia trachomatis infection among women with pelvic inflammatory disease (PID). METHODS: We tested whether 18 tagging single nucleotide polymorphisms (tagSNPs) assayed in 4 TLR genes (TLR1, TLR2, TLR4, TLR6) and 2 adaptor molecules (TIRAP, MyD88) were associated with C. trachomatis among 205 African American women with clinically suspected PID from the PID Evaluation and Clinical Health Study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). An empirical P value of <.004 was considered significant. RESULTS: Women with PID who carried the TLR4 rs1927911 CC genotype had significantly increased odds of C. trachomatis (OR, 3.7; 95% CI, 1.6-8.8; P = .002). The TLR1 rs5743618TT genotype was also associated with C. trachomatis (OR, 2.8; 95% CI, 1.3-6.2; P = .008). CONCLUSIONS: Among African American women with PID, variants in the TLR1 and TLR4 genes, which may increase signaling, were associated with increased C. trachomatis infection.

The role of Chlamydia trachomatis polymorphic membrane proteins in inflammation and sequelae among women with pelvic inflammatory disease.

Chlamydia trachomatis polymorphic membrane proteins (Pmps) may increase genital tract inflammation and play a role in virulence. Antibody levels for PmpA, PmpD, and PmpI, measured in densitometric units, were assessed among a pilot sample of 40 C. trachomatis-infected women with mild-to-moderate clinical PID. Women who expressed antibodies to PmpA were less likely to achieve pregnancy (40.0% versus 85.7%; P = 0.042) and less likely to have a live birth (0.0% versus 80.0%; P = 0.005) compared to women who did not express antibody to PmpA. Women who expressed antibodies to PmpI were more likely to have upper genital tract infection (61.5% versus 20.0%; P = 0.026). However, seropositivity to PmpI and PmpD did not modify the risk of reproductive sequelae or inflammation. Seropositivity to chlamydial PmpA may represent a biomarker of increased risk of sequelae secondary to infection with C. trachomatis.

Relationships between transvaginal colour Doppler findings, infectious parameters and visual analogue scale scores in patients with mild acute pelvic inflammatory disease.

OBJECTIVE: To investigate the relationships between colour Doppler findings, infectious parameters and visual analogue scale (VAS) scores in patients with mild acute pelvic inflammatory disease (PID). STUDY DESIGN: Twenty-seven patients diagnosed with PID were enrolled in the study. Resistance index (RI) and pulsatility index (PI) of uterine, arcuate and utero-ovarian arteries were measured, as well as VAS score, erythrocyte sedimentation rate, C-reactive protein, white blood cell count and body temperature at hospital admission. After the initial visit, all measurements were repeated and recorded on days 7, 15 and 30. RESULTS: PI and RI values of uterine arteries showed significant increases between days 1 and 7. However, PI and RI values of uterine arteries, RI values of arcuate arteries and RI values of utero-ovarian arteries showed significant increases between days 1 and 30. Statistically significant decreases in infectious parameters and VAS scores were observed between days 1 and 7, days 1 and 15 and days 1 and 30. CONCLUSION: Infectious parameters and VAS scores showed concordant changes with clinical recovery in mild PID. Significant changes were also observed in PI and RI values of uterine arteries, but Doppler measurements of arcuate and utero-ovarian arteries showed a slower and later response to treatment.