Chlamydial Pelvic Inflammatory Disease Research Articles

Chlamydia infection, PID, and infertility: further evidence from a case–control study in China

BackgroundChlamydia trachomatis infection and pelvic inflammatory disease (PID) are well-known risk factors for female infertility. But there is limited evidence from China. This study aimed to further explore the associations between previous/current chlamydial infection, PID, and infertility in China.MethodsWe performed a 1:2 matched case–control study with two control groups: pregnant controls and non-pregnant controls in China in 2019. Women diagnosed with infertility were selected as cases (n = 255). Controls were selected based on the following criteria: Pregnant women who were documented in the selected hospitals were chosen as Pregnant controls (n = 510), and people who sought health care in Obstetric/Gynecologic clinics, Family Planning clinics, Dermatology and STD Department or Urological department were selected as Non-pregnant controls (n = 510). Infertility induced by male factors and people who used antibiotics in the vagina within two weeks were excluded. The first-stream specimen of urine samples was tested for chlamydia by nucleic acid amplification testing (NAAT). Conditional logistic regression was used to estimate the association.ResultsThe prevalence of previous chlamydial infection and PID were significantly higher in cases (2.4%, 17.3%) than in controls (Non-pregnancy: 0.4%, 3.0%; Pregnancy: 0.4%, 9.0%). The current chlamydial infection rates were 5.9%, 7.3%, and 7.1% in infertile, pregnant, and non-pregnant women, respectively. After adjusting for confounders, PID largely elevated the risk of infertility (using non-pregnant controls: adjusted OR = 2.57, 95% CI 1.51, 4.39; using pregnant controls: adjusted OR = 6.83, 95% CI 3.47, 13.43). And the positive association between PID and tubal infertility was more obvious for both groups. For current chlamydial infection, none of the odds ratios were significant at the 0.05 level, while small sample size limited the evaluation of an association between prior chlamydial infection with infertility.ConclusionsPrevious PID was indicated to largely increase the risk of infertility, especially tubal infertility. And there should be continuing emphasis on highly sensitive and specific biomarker for prior chlamydial infection.

Chlamydia trachomatis, Pelvic Inflammatory Disease, and Epithelial Ovarian Cancer.

Epidemiologic, clinical, molecular and translational research findings support an interrelationship between Chlamydia trachomatis, pelvic inflammatory disease (PID), and epithelial ovarian cancer (EOC). Overall, the link between C. trachomatis, PID, and EOC seems to be relatively weak, although nondifferential misclassification bias may have attenuated the results. The predominant tubal origin of EOC and the role of chronic inflammation in tumorigenesis suggest that the association is biologically plausible. Thus, C. trachomatis and PID may represent potential risk factors or risk markers for EOC. However, many steps in this chain of events are still poorly understood and need to be addressed in future studies. Research gaps include time of exposure in relation to the long-term consequences and lag time to EOC. Data of differential risk for EOC between chlamydial and nonchlamydial PID is also needed. Another major research gap has been the absence of high-performance biomarkers for C. trachomatis, PID, and EOC, as well as EOC precursors. Biomarkers for C. trachomatis and PID leading to increased risk of EOC should be developed. If the association is confirmed, C. trachomatis and PID prevention efforts may play a role in reducing the burden of EOC.

Utility of Ascitic Fluid Adenosine Deaminase Levels in the Diagnosis of Tuberculous Peritonitis in General Medical Practice.

Background Tuberculous peritonitis is difficult to diagnose due to its varying clinical features, in addition to the low yield on bacterial culture or polymerase chain reaction using ascitic fluid samples. This study aimed to investigate the sensitivity and specificity of elevated adenosine deaminase (ADA) levels as a diagnostic marker for tuberculous peritonitis. Methods A retrospective cohort of 181 adult patients who underwent ascitic fluid ADA level examination at Jichi Medical University Hospital between January 2006 and December 2015 were included. We collected data regarding ascitic fluid analyses including ADA levels, bacteriology and cytology, final diagnosis (cause of ascites), basis of the diagnosis, duration to diagnosis, and disease outcome. Results Among 181 patients, elevated ascitic ADA levels (≥40 IU/L) were observed in 15 patients (median, 87.2 IU/L; range, 44.0–176.1 IU/L); 8 patients had tuberculous peritonitis, 4 had lymphoma-related ascites, and 2,had peritoneal carcinomatosis with bacterial coinfection, and 1 had chlamydial pelvic inflammatory disease. Among 166 patients without ascitic ADA level elevation (median, 7.3 IU/L; range, <2.0–39.1 IU/L), none had tuberculosis, 4 had lymphoma-related ascites, 28 had cancer/mesothelioma-related ascites, and 134 had ascites due to other causes. In our cohort, elevated ascitic fluid ADA levels (≥40 IU/L) showed 100% sensitivity, 96.0% specificity, 53.3% positive predictive value (PPV), and 100% negative predictive value for the diagnosis of peritoneal tuberculosis. Conclusions Ascitic fluid ADA levels ≥40 IU/L showed excellent sensitivity, despite a low PPV, for the diagnosis of tuberculous peritonitis. Lymphoma-related ascites is an important mimic of tuberculous peritonitis that can result in high ascitic fluid ADA levels with similar clinical manifestations.

Clinical Features and Therapeutic Response in Women Meeting Criteria for Presumptive Treatment for Pelvic Inflammatory Disease Associated With Mycoplasma genitalium.

There are limited published data describing clinical features and therapeutic response in women meeting the criteria for presumptive treatment of pelvic inflammatory disease associated with Mycoplasma genitalium (MG-PID). The MG-PID has been reported to respond poorly to standard PID treatment regimens and while moxifloxacin is recommended in several treatment guidelines, published data to support its use are scant. We conducted a retrospective study of women at Melbourne Sexual Health Centre between 2006 and 2017, who met the Centers for Disease Control and Prevention criteria for presumptive treatment of PID, and had MG detected as the sole pathogen. Clinical and laboratory characteristics of MG-PID were compared to cases of chlamydial PID (CT-PID) by multivariable analysis. Microbiological and clinical cure following moxifloxacin and standard PID treatment was determined for women with MG-PID who returned for test of cure between 14 and 120 days. Ninety-two patients with MG-PID were compared with 92 women with CT-PID. The MG-PID was associated with increased lower abdominal tenderness (adjusted odds ratio, 2.29; 95% confidence interval [CI], 1.14-4.60), but a lesser vaginal polymorphonuclear response compared to CT-PID by multivariable analysis. Of the 92 women with MG-PID, 54/92 (59%) received moxifloxacin (10-14 days) and 37/54 had a test of cure between 14 and 120 days; 27/37 (73%) cases had a median of 7 days of a standard regimen containing doxycycline and metronidazole +/- azithromycin before moxifloxacin. Microbial cure following moxifloxacin was 95% (95% CI, 82-99%) and did not differ from standard therapy (P = 0.948), however clinical cure was significantly higher following moxifloxacin (89%; 95% CI, 75-97%; P = 0.004)] although adverse effects were more common. Women meeting Centers for Disease Control and Prevention criteria for presumptive treatment of MG-PID did not significantly differ to those with CT-PID. Moxifloxacin was associated with higher rates of symptom resolution in women with PID, and although microbial cure was high, it did not differ between regimens.

Gonococcal and Chlamydial Cases of Pelvic Inflammatory Disease at 2 Canadian Sexually Transmitted Infection Clinics, 2004 to 2014: A Retrospective Cross-sectional Review.

One hundred thirteen patients with gonococcal and chlamydial pelvic inflammatory disease were reviewed at 2 Canadian sexually transmitted infection clinics. Most patients (81%) with pelvic inflammatory disease were diagnosed as having chlamydia alone. Three treatment failures were seen in patients treated with ofloxacin.

Whole-Exome Sequencing to Identify Novel Biological Pathways Associated With Infertility After Pelvic Inflammatory Disease.

Ideal management of sexually transmitted infections (STI) may require risk markers for pathology or vaccine development. Previously, we identified common genetic variants associated with chlamydial pelvic inflammatory disease (PID) and reduced fecundity. As this explains only a proportion of the long-term morbidity risk, we used whole-exome sequencing to identify biological pathways that may be associated with STI-related infertility. We obtained stored DNA from 43 non-Hispanic black women with PID from the PID Evaluation and Clinical Health Study. Infertility was assessed at a mean of 84 months. Principal component analysis revealed no population stratification. Potential covariates did not significantly differ between groups. Sequencing kernel association test was used to examine associations between aggregates of variants on a single gene and infertility. The results from the sequencing kernel association test were used to choose "focus genes" (P < 0.01; n = 150) for subsequent Ingenuity Pathway Analysis to identify "gene sets" that are enriched in biologically relevant pathways. Pathway analysis revealed that focus genes were enriched in canonical pathways including, IL-1 signaling, P2Y purinergic receptor signaling, and bone morphogenic protein signaling. Focus genes were enriched in pathways that impact innate and adaptive immunity, protein kinase A activity, cellular growth, and DNA repair. These may alter host resistance or immunopathology after infection. Targeted sequencing of biological pathways identified in this study may provide insight into STI-related infertility.

Co-expression network analysis reveals immune response pathways important for pathogenesis of Chlamydial pelvic inflammatory disease (PID). (HUM8P.329)

Abstract Processes driving development of immune pathology after Chlamydia trachomatis infection are poorly understood. To provide insight into the pathways that may be underappreciated by individual gene analysis, weighted gene co-expression network analysis was performed to identify network modules using blood transcriptional profiles of women with chlamydial PID (N=15) and asymptomatically infected women (N=84). Modules, defined as centrally connected genes, that were significantly associated with chlamydial PID were further accessed via Ingenuity Pathway analysis. Type I and type II interferon (IFN) signaling pathways were significantly up regulated in women with chlamydial PID. Up regulation of both of these pathways has been detected in the transcriptomes of patients with active tuberculosis, suggesting a parallel role in PID. Up regulation of aryl hydrocarbon receptor, agranulocyte/granulocyte adhesion and diapedesis pathways was also noted, while EIF2/EIF4, mTOR and ILK signaling, granzyme A/B signaling, cross talk between dendritic cells and natural killer cells, signaling in T helper cells and T cell receptor pathways were down-regulated. Pathways likely to contribute to immunopathogenesis, including migration of leukocytes and inflammation were activated in chlamydial PID, while those involved in cell growth/proliferation and clearance of infected cells were decreased. Bioinformatics provides a new avenue to improve understanding of chlamydial disease mechanisms.

O01.4 Blood Transcriptional Profiling of Women with Chlamydia Trachomatis Identifies a Pelvic Inflammatory Disease (PID) Signature

ObjectiveMost women with Chlamydia trachomatis (CT) infection are asymptomatic, while ∼3% progress to pelvic inflammatory disease (PID) within two weeks of untreated infection. The identification of biomarkers that predict development...

Nonhuman primate models used to study pelvic inflammatory disease caused by Chlamydia trachomatis.

Pelvic inflammatory disease (PID) is a global health concern that is associated with significant morbidity and is a major cause of infertility. Throughout history animals have been used for anatomical studies and later as models of human disease. In particular, nonhuman primates (NHPs) have permitted investigations of human disease in a biologically, physiologically, and anatomically similar system. The use of NHPs as human PID models has led to a greater understanding of the primary microorganisms that cause disease (e.g., Chlamydia trachomatis and Neisseria gonorroheae), the pathogenesis of infection and its complications, and the treatment of people with PID. This paper explores historical and contemporary aspects of NHP modeling of chlamydial PID, with an emphasis on advantages and limitations of this approach and future directions for this research.

The demographic, sexual health and behavioural correlates of Mycoplasma genitalium infection among women with clinically suspected pelvic inflammatory disease

ObjectiveMycoplasma genitalium has been identified as a cause of pelvic inflammatory disease (PID), a clinical syndrome associated with inflammation of the female upper genital tract and serious reproductive sequelae. As...

Clinical Presentation ofMycoplasma genitaliumInfection versusNeisseria gonorrhoeaeInfection among Women with Pelvic Inflammatory Disease

Women with pelvic inflammatory disease (PID) often present with a spectrum of symptoms. The characteristics of nongonococcal, nonchlamydial PID have not been well described. Our objective was to examine the characteristics of Mycoplasma genitalium infection among women with clinically suspected PID. We evaluated 722 women who were enrolled in the PID Evaluation and Clinical Health study. Women with M. genitalium monoinfection were compared with women with Neisseria gonorrhoeae monoinfection or Chlamydia trachomatis monoinfection. Compared with women with gonococcal PID, women with M. genitalium infection were less likely to have elevated systemic inflammatory markers, including an erythrocyte sedimentation rate >15 mm/h (5 [22.7%] of 22 patients vs. 45 [60.8%] of 74 patients; P = .002), a white blood cell count >10,000 cells/mL (4 [28.6%] of 14 patients vs. 42 [64.6%] of 65 patients; (P = .018), and an oral temperature > or =38.3 degrees C (0 [0.0%] of 22 patients vs. 10 [13.9%] of 72 patients; (P = .001). In addition, they were less likely to present with mucopurulent cervicitis (9 [47.4%] of 19 patients vs. 60 [83.3%] of 72 patients; P = .001), elevated vaginal pH (P = .018), and high pelvic pain score (P = .014). In contrast, women with chlamydial PID had signs and symptoms that were similar to those in women with M. genitalium infection. Because symptoms might be mild, women with M. genitalium infection might not seek PID treatment. Further studies are needed to assess the potential reproductive tract sequelae of M. genitalium infection of the upper genital tract.

Autoimmune response to Chlamydia trachomatis infection and in vitro fertilization outcome

This observational study was conducted in 235 patients undergoing IVF who had a cervical swab positive for Chlamydia trachomatis and who underwent antibiotic treatment until a negative cervical swab before IVF attempt. After oocyte retrieval, follicular fluids of 109 patients out of 228 still showed the presence of IgA antichlamydia antibodies and a significantly lower pregnancy and implantation rate; therefore we conclude that patients should undergo IVF procedure after serum antichlamydia IgA tests negative.

A case of chlamydial pelvic inflammatory disease with edematous swelling and softening of the ovaries observed under laparoscopic surgery

Sexually transmitted diseases involving chlamydia are increasing, and sterility as a chronic sequela of chlamydial infection appears to be on the rise. Prevention of progression and sequelae is possible if appropriate antibacterial drugs are given during the early period of infection. However, many cases develop so-called silent pelvic inflammatory disease (silent PID), which progresses asymptomatically from cervicitis to abdominal cavity infection. While recently performing laparoscopic ovarian drilling to treat a patient with polycystic ovary syndrome (PCOS), we observed edematous swelling and softening of bilateral ovaries. Two months later, the patient developed a large quantity of ascites and a high CA125 level. Therefore, the patient underwent further investigation and antibacterial therapy was started. The ascites disappeared soon after antibacterial treatment was given. The clinical test results and the typical filmy adhesions around the adnexa observed on subsequent laparoscopy confirmed that this patient's clinical course was due to chlamydial PID.

Chlamydia trachomatisSerology in Women with and without Ovarian Cancer

Pelvic inflammation has been implicated in the genesis of ovarian cancer. We conducted serologic measurements of Chlamydia trachomatis antibodies as a surrogate marker of chlamydial pelvic inflammatory disease. Women with ovarian cancer (n = 521) and population-based controls (n = 766) were tested. IgG antibodies to serovar D of chlamydia elementary bodies (EBs) were detected using an ELISA assay. The odds of having ovarian cancer among women with the highest titers (≥0.40 OD units) were 0.6 (95% CI 0.4–0.9). These data do not support our earlier finding of elevated titers for antibodies to C. trachomatis among women with ovarian cancer.

Treatment of Pelvic Inflammatory Disease

A few data are clear regarding the treatment of pelvic inflammatory disease (PID). First, antibiotics are better than no antibiotics [1]. Second, chlamydial PID produces more long-term sequelae than does PID caused by other microbes [2], in part because Chlamydia trachomatis produces few clinical signs, and there is late clinical recognition of the infection. Third, to date, within a given etiologic group, the duration of symptoms (and not the particular antibiotic regimen) appears to be the largest determinant of infertility [3, 4]. Fourth, the recommendation from the Centers for Disease Control and Prevention that treatment needs to be effec-

Significant reduction in inflammatory response in the macaque model of chlamydial pelvic inflammatory disease with azithromycin treatment.

We inoculated 45 female macaques in the cervix with Chlamydia trachomatis once weekly for 5 weeks and randomly assigned them to treatment with doxycycline (n=12), azithromycin (n=12), or placebo (n=21). At hysterectomy, cervical cultures remained positive in 12 of 21 placebo-treated monkeys, versus 0 of 12 doxycycline- or azithromycin-treated monkeys (P<.01); cervical ligase chain reaction remained positive in 15 placebo-, 1 doxycycline-, and 0 azithromycin-treated monkeys. Tubal swabs remained positive in 3 placebo-, 1 doxycycline-, and 0 azithromycin-treated monkeys. Immunopathologic damage was moderate to widespread in upper and lower reproductive-tract tissues from placebo- and doxycycline-treated monkeys but were significantly reduced in azithromycin-treated monkeys. Transforming growth factor- beta was also significantly less prevalent in azithromycin-treated monkeys. Azithromycin treatment dramatically reduced the inflammatory response and was highly effective in eradicating C. trachomatis from the lower and upper reproductive tract (12/12), compared with doxycycline (7/12) and placebo (3/21).

Epidemiological and Genetic Correlates of IncidentChlamydia trachomatisInfection in North American Adolescents

Epidemiological and genetic correlates of Chlamydia trachomatis infection were examined prospectively in 124 male and 361 female adolescents at high risk for human immunodeficiency virus type 1 (HIV-1) infection. Seventy percent of subjects were African American, and 68% had HIV-1 infection. As expected, younger age (<17 years), multiple sex partners (> or =2), and prior chlamydial infection predicted chlamydial infection during a 6-56-month follow-up period (P=.02, P=.02, and P=.03, respectively). Human leukocyte antigen (HLA) class II variant DQB1*06 (mostly *0602 and *0603) was associated with chlamydial infection (49% vs. 34%; adjusted relative odds [RO], 1.8; P=.005), as was HLA class I haplotype B*44-Cw*04 (10% vs. 4%; RO, 3.2; P=.009). DQB1*06 was found in 9 (75%) of 12 female adolescents with chlamydial pelvic inflammatory disease. In contrast, sex, ethnicity, and HIV-1 infection did not predict chlamydial infection. These findings suggest that antigen presentation in adaptive immune responses may serve as a major factor in effective control of C. trachomatis infection. The underlying mechanisms remain to be experimentally elucidated.

A multidistrict audit of the management of chlamydial PID in genitourinary medicine clinics in Yorkshire.

In response to recent reviews of practice of pelvic inflammatory disease (PID) management, a multidistrict audit involving eight genitourinary clinics within the Yorkshire region was carried out. This audit reports the referral patterns of patients, physical signs and microscopy findings at the first genitourinary medicine (GUM) clinic attendance, antibiotic treatment and follow-up data as well as health adviser involvement and partner participation for 68 patients diagnosed with chlamydial PID. Twenty-eight (41.2%) patients presented with symptoms of less than or equal to four weeks duration, partner notification was recorded as being carried out for all patients and at least one partner was documented as having been treated in 57 (83.8%) patients. There is, however, a wide variation in the antibiotic regimens used for treatment and their duration.

Chlamydia trachomatis infections - a major concern for reproductive health. Where do we stand regarding epidemiology, pathogenesis, diagnosis and therapy?

The current article deals with the problem of distinguishing between relapse and reinfection of genital chlamydial infections due to the chronic character of such infections. The problem of detecting and treating chlamydial pelvic inflammatory disease is considered. Factors that may affect the clinical presentation of such infections, such as hormonal therapy, are also highlighted. Observations on novel manifestations of Chlamydia trachomatis infections, such as spontaneous abortion, prematurity and intrauterine infections as well as a statistical correlation of a certain serovar to cervical cancer, are described. The representivity of the data on infections with C. trachomatis monitored in national surveillance programs is questioned. The paper also elaborates on which type of sample, sample site and detection method may be optimal for the diagnosis of such infections in women. Whether to screen at clinics and self-sampling at home of specimens from an index case and a sexual partner to be mailed to a laboratory for testing is discussed. Whether or not females are more susceptible to genital chlamydial infections and their sequelae than males is also discussed. The effectiveness of recommended antibiotic regimens is considered, e.g. in relation to the recent detection of the existence of strains of C. trachomatis that show heterotypic resistance to drugs commonly used for their treatment.

Chlamydia trachomatis infections – a major concern for reproductive health. Where do we stand regarding epidemiology, pathogenesis, diagnosis and therapy?

The current article deals with the problem of distinguishing between relapse and reinfection of genital chlamydial infections due to the chronic character of such infections. The problem of detecting andtreating chlamydial pelvic inflammatory disease is considered. Factors that may affect the clinical presentation of such infections, such as hormonal therapy, are also highlighted. Observations on novelmanifestations of Chlamydia trachomatis infections, such as spontaneous abortion, prematurity and intrauterine infections as well as a statistical correlation of a certain serovar to cervical cancer,are described. The representivity of the data on infections with C. trachomatis monitored in national surveillance programs is questioned. The paper also elaborates on which type of sample, samplesite and detection method may be optimal for the diagnosis of such infections in women. Whether to screen at clinics and self-sampling at home of specimens from an index case and a sexual partner to bemailed to a laboratory for testing is discussed. Whether or not females are more susceptible to genital chlamydial infections and their sequelae than males is also discussed.The effectiveness of recommendedantibiotic regimens is considered, e.g. in relation to the recent detection of the existence of strains of C. trachomatis that show heterotypic resistance to drugs commonly used for their treatment.