Gonococcal Pelvic Inflammatory Disease Research Articles

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.

Gonococcal Pelvic Inflammatory Disease with Sepsis Criteria: Review of 2 Cases

Background: Infection caused by Neisseria Gonorrhoeae increases the risk of pelvic inflammatory disease (PID). Gonococcal PID tends to be clinically more severe than non-gonococcal ones. The main is to present two cases of gonococcal PID, with rapid clinical and analytic progression, leading to severe sepsis, but without imaging manifestations. Clinical presentation: 1. 41-year-old patient with replacement of intrauterine releasing levonorgestrel device (IUD), presented abdominal pain and green vaginal discharge. Abdominal examination revealed signs of peritoneal irritation and blood test showed leukocytosis, increased C Reactive Protein and procalcitonin, as well as coagulation abnormalities. Imaging tests (vaginal ultrasound/tomography) revealed no structural pathology, without collections. Given the criteria of severe sepsis, broadspectrum intravenous (iv) antibiotic therapy was started and laparoscopy and IUD removal were performed. Cervical and IUD cultures were positive for Neisseria gonorrhoeae. 2. 20-year-old woman, with an IUD, consulted for abdominal pain, low-grade fever and green vaginal discharge. Abdominal examination suggested peritoneal sensitivity and laboratory tests leukocytosis, increased C Reactive Protein and procalcitonin with coagulation abnormalities. Imaging tests (vaginal ultrasound/tomography) showed no structural pathology, without collections. Despite analgesia and broad-spectrum iv antibiotics, the patient worsened, proceeding to remove the IUD. Given the criteria compatible with severe sepsis, laparoscopy was decided. Endocervical and IUD cultures revealed Neisseria gonorrhoeae. Conclusions: Facing the situation of an acute PID with severe and fast clinical worsening even without findings in imaging tests, we should consider gonococcal ethiology as a possible cause. Surgical approach shouldn’t be delayed in order to control the infection and rule out other possible diagnosis.

Intrauterine Devices in the Context of Gonococcal Infection, Chlamydial Infection, and Pelvic Inflammatory Disease: Not Mutually Exclusive.

The use of long-acting reversible contraception, namely, intrauterine device (IUDs) and the subdermal implant, has been recommended to address the high rate of the unintended pregnancy in the United States. IUDs are a safe, highly effective contraceptive method, suitable for most women. The underutilization of IUDs arises in part from the lack of translation of best practices in the clinical setting as well as fears and misperceptions about this contraceptive method held by health care providers and women. This article reviews screening and management of Neisseria gonorrhoeae and Chlamydia trachomatis infection and pelvic inflammatory disease (PID) in women who are using or want to use an IUD. An IUD may be inserted without prior screening for N gonorrhoeae or C trachomatis in women who are at low risk for sexually transmitted infections and asymptomatic. An in situ IUD may remain in the uterus during and after treatment for gonococcal infection, chlamydial infection, or PID. The risk of PID with an IUD in situ is less than 1%. Following IUD best practices, including their use in the context of sexually transmitted infections, can increase the availability of this method for suitable candidates and decrease the unintended pregnancy rate.

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.

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.

O25 Use of ceftriaxone and doxycycline when treating gonorrhoea: is it prescribed appropriately?

Background National gonorrhoea treatment guidelines recommend ceftriaxone with azithromycin as first-line therapy, but doxycycline is recommended instead of azithromycin for patients with gonococcal pelvic inflammatory disease (PID). In 2013, 86.5% of patients in the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) were treated with the recommended therapy, but 3.9% were treated with doxycycline instead of azithromycin. Objectives The objective of this analysis was to determine whether ceftriaxone plus doxycycline were prescribed for appropriate indications. Methods Using GRASP 2013 data, patients prescribed the recommended therapy were compared with patients prescribed ceftriaxone and doxycycline, and associations were assessed using univariate and multivariate logistic regression. Results In 2013, of the 913 patients prescribed ceftriaxone and azithromycin, 45.9% were men who have sex with men (MSM), 20% were women and 34.1% were heterosexual men while, of the 45 patients prescribed ceftriaxone and doxycycline, 64.4% were MSM, 28.9% were women and 6.7% were heterosexual men (p = 0.001). Of those prescribed ceftriaxone and doxycycline, 22.2% were MSM with chlamydia co-infection and 17.7% were women with PID. On multivariate analysis, MSM co-infected with chlamydia (aOR 3.4, 95% CI, 2.5–4.6; p = 0.001) and women diagnosed with gonococcal PID (OR,144.8, 95% CI, 24.2–864.0; p Conclusion Less than a fifth of prescriptions for ceftriaxone with doxycycline were issued to treat gonococcal PID. Use of ceftriaxone with doxycycline may be preferred to treat MSM co-infected with chlamydia by some clinicians. However, as levels of tetracycline resistance in gonorrhoea are high, this may not provide the dual treatment coverage required.

P61 IM ceftriaxone for all pelvic inflammatory disease: to give or not to give?

AimTo audit the care of Pelvic Inflammatory Disease (PID) in a city centre Genitourinary medicine clinic.Objectives(1) To assess the effectiveness of PID treatment offered by evaluating the auditable outcomes recommended...

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...

Gonorrheal Infection, Pelvic Inflammatory Disease and Spinal Disability

Gonorrheal infection is an important sexually transmitted disease. Neisseria gonorrhoeae is responsible for about one-third to one-half of cases of acute pelvic inflammatory disease (PID). Spinal osteochondrosis is an important complication of chronic gonococcal PID. Rehabilitative intervention plays an important role for coping with this condition. In addition to gonococcal PID, congenital gonorrhea and gonococcal prostatitis are the other two important conditions that relate to spinal disability.

Pelvic inflammatory disease and tubal infertility: the preventable conditions.

There are three clear links in the causal pathway for pelvic inflammatory disease (PID): lower genital tract sexually transmitted disease (STD) followed by upper genital tract PID and then tubal infertility. This pathway also entails two clear relationships that have a temporal lag in clinical expression: STD leading to PID and PID leading to tubal infertility. The genital microbial environment the individual behavioral environment (e.g. sexual behavior) and the sociogeographic environment have overlapping effects on these relationships. Neisseria gonorrhoeae Chlamydia trachomatis and anaerobic bacteria are the most common pathogens associated with upper genital tract infection. STD organisms initially infect the cervix endometrium and tubal mucosa and prepare the tissue for subsequent polymicrobial infection. A concurrent prolonged inflammatory response and latent chlamydia infection of the endometrium and/or fallopian tube may further predispose infection with aerobic and anaerobic bacteria. The anaerobic bacteria cause damage by both direct effects of virulence factors and secondary effects on host defenses. Risk factors for PID and infertility include age contraceptive choice and cigarette smoking. Other PID risk factors are race frequency of intercourse timing of coitus sex practices age of onset of sexual activity previous episodes of gonococcal PID and douching. Other risk factors for infertility are number of previous PID episodes severity of pelvic inflammation and chlamydia infection. Asymptomatic PID accounts for more than 50% of all PID cases. Atypical symptoms (e.g. oligomenorrhea) or biochemical (e.g. metabolic or immunologic) markers may need to be used to identify PID. Tubal infertility occurs in 10-30% of couples seeking infertility services in developed countries. All studies show a strong relationship between STD/PID and infertility. The pathogenesis of infertility includes postinfectious scarring microbiologic virulence and host immune factors. The most cost effective way to reduce tubal infertility is prevention of lower genital tract STDs.

Pelvic inflammatory disease

Pelvic inflammatory disease is a common serious complication of the sexually transmitted pathogens Neisseria gonorrhoeae and Chlamydia trachomatis. There are more than 800,000 cases of pelvic inflammatory disease annually accounting for approximately 200,000 hospital admissions for acute and chronic infections. Early accurate diagnosis and treatment are essential to prevent the serious sequelae including ectopic pregnancy, tubal disease infertility, chronic pain, and disability requiring multiple hospitalizations and surgery. Although clinical models to aid in the diagnosis and management of pelvic inflammatory disease have been developed by numerous investigators, all have lacked the sensitivity and specificity to be helpful to the clinician. Laparoscopy, considered by many to be the "gold standard" for diagnosis, is underutilized, and the definition of pelvic infection differs between investigators. Improved patient compliance and safety may be seen if single-agent therapy for acute pelvic inflammatory disease becomes a reality. In a small prospective randomized study, oral ofloxacin was as effective as cefoxitin plus doxycycline for outpatient treatment of chlamydial and gonococcal pelvic inflammatory disease. Treatment of tuboovarian abscess appears to be successful with single agent and combination therapy. Risk factors for developing postabortion endometritis continue to be identified, and the most efficacious prophylactic antibiotic regimen has not been determined to date.

Acute pelvic inflammatory disease in adolescents

Timely diagnosis and early treatment of pelvic inflammatory disease (PID) in the adolescent is essential, as it occurs with great frequency in this age group, and may result in severe long-term morbidity, including infertility.Study Objective: Previous reports have described that the onset of symptoms in this illness typically begins within the first week of the menstrual cycle. This study was undertaken to determine the relationship between timing of symptom onset and the bacterial etiology of acute PID in female adolescents.Design: A retrospective chart review was performed on 164 inpatients (mean age 19 years old) with the diagnosis of PID, and data were analyzed based on whether the patients were infected with gonorrhea, chlamydia, neither of these bacteria, or both.Results: Eighty-three percent of the patients with gonorrhea had onset of symptoms within the first menstrual week, which was significantly greater than those with chlamydia (31.7%) p = 0.004, or those with neither (29.7%) p = 0.001. Patients with concurrent gonorrhea and chlamydia developed symptoms on the average of menstrual cycle day 12. A greater proportion of those positive for gonorrhea had a leukocyte count > 10,000 than the other three groups (p = 0.02), but 33–71% of patients in all groups had a normal leukocyte count. Temperature and sedimentation rate were not helpful in distinguishing the bacterial etiology of the PID.Conclusions: Among adolescents, only gonococcal PID results in onset of symptoms within the first week after onset of menses whereas nongonococcal disease occurs significantly later. Fever and leukocytosis are inconsistently present with PID. Their absence, therefore, should not discourage consideration of this diagnosis.

Class specific antibody response to gonococcal infection.

An enzyme immunoassay was used to determine IgM, IgG, and IgA antibodies to gonococcal pili in 68 patients with uncomplicated gonorrhoea, 35 women with pelvic inflammatory disease, and in 115 normal controls. A clear difference in response rate in all three antibody classes between patients with gonorrhoea and healthy controls was evident. Among women with gonorrhoea, the magnitude of antibody response was higher than among men with gonorrhoea, especially in the IgM class. No major differences were found in the overall distribution of serological findings between women with uncomplicated gonorrhoea and those with gonococcal pelvic inflammatory disease. Among this last group, however, high IgM antibody levels in acute phase sera were significantly associated with the isolation of Neisseria gonorrhoeae in the upper genital tract.

Treating pelvic inflammatory disease with doxycycline and metronidazole or penicillin and metronidazole.

The best way of treating pelvic inflammatory disease (PID) is not known. The clinical response to two treatment regimens (penicillin plus metronidazole v doxycycline plus metronidazole) was studied in 33 patients with PID confirmed by laparoscopy and endometrial biopsy. The overall failure rate, according to the criteria used in this study was five of 11 (45%) women with chlamydial PID, none of six women with gonococcal PID, all of four women with chlamydial gonococcal PID, and three (25%) of 12 women with non-chlamydial non-gonococcal PID. The failure rate with penicillin plus metronidazole treatment was unacceptably high (53%), and significantly higher than that with doxycycline plus metronidazole (19%) (p = 0.038). In most cases the microbiological and histopathological evaluations identified a probable explanation for the poor response to the treatment regimen used.

Comparison of the clinical and epidemiologic characteristics of gonococcal and nongonococcal pelvic inflammatory disease seen in a clinic for sexually transmitted diseases, 1978-1979.

Despite the magnitude of the clinical and economic impact of pelvic inflammatory disease (PID), little is known about its outpatient presentation. We compared retrospectively the clinical and epidemiologic characteristics of 70 women with gonococcal PID, 44 women with nongonococcal PID, and 8,576 control women without PID seen in a clinic for sexually transmitted diseases. Gonococcal PID was associated with black race (P less than .002) and a shorter period of abdominal pain (P less than .02). Nongonococcal PID was associated with white race (P less than .005) and a history of previous gonococcal infection (P less than .02). There were no significant differences between groups in age, parity, number of sexual partners, contraceptive use, or febrility. PID seen in women attending our outpatient clinic is often mild, and the diagnosis uncertain. We found few reliable indicators to aid in the clinical diagnosis or to distinguish etiology. More studies are needed to improve the outpatient management of PID and limit its impact.

Antibody-Antigen Specificity in the Immune Response to Infection with Neisseria gonorrhoeae

This study was done to define antigens important in the immune response to infection with Neisseria gonorrhoeae. Sera were obtained from men and women with uncomplicated gonorrhea (UGC), women with disseminated gonococcal infection, and women with gonococcal pelvic inflammatory disease (PID); sera were also obtained from uninfected controls. Vaginal fluids were taken from 15 patients with UCG or PID. The sera and vaginal fluids were tested against gonococcal isolates from the same patients to examine homologous antibody-antigen interactions by use of the western blot technique. Antibodies in the serum reacted with more gonococcal antigens compared with antibodies in the vaginal fluid. IgG in serum and vaginal fluid reacted with more antigens than did IgA in the same specimens. The predominant antigens reactive with IgG in serum were pili, protein II, a broad 23-33-kDa band of antigen, and presumptive lipopolysaccharide; and for IgA, protein II and a 46-48-kDa protein. The control sera also reacted with the 46-48-kDa protein. The predominant antigens reactive with IgG in vaginal fluid were protein I, protein II, pili, and the 46-48-kDa protein; and for IgA, protein I, protein II, and pili. Immunoglobulin in vaginal fluid reacted comparatively more with protein I than did immunoglobulin in serum.

Oral Contraceptives, Chlamydia trachomatis Infection, and Pelvic Inflammatory Disease

Management of pelvic inflammatory disease (PID) and decisions about contraception are being influenced by reports that oral contraceptives decrease the risk of PID. To evaluate the validity of this association, we have examined published epidemiologic evidence and reviewed relevant information from other disciplines. Current information does not permit the generalization that oral contraceptives protect against all forms of PID. Most studies conducted (1) have been limited to hospitalized women, who represent less than 25% of all PID cases and are likely to have relatively severe forms of the disease, and (2) have failed to distinguish between gonococcal and nongonococcal PID. While oral contraceptives may provide some protection against gonococcal PID, no basis exists for assuming similar protection is provided against chlamydial PID. In fact, epidemiologic and biologic evidence suggests that infection with Chlamydia trachomatis, the leading cause of nongonococcal PID, is enhanced by oral contraceptives. We judge the conclusion that oral contraceptives protect against all PID to be premature, and urge caution in its application in health policy and clinical decisions.

Epidemiology of Sexually Transmitted Diseases

In the past decade, the recognized spectrum of sexually transmitted diseases has widened to a complex array of agents and syndromes. The authors correlate diseases with responsible pathogens and discuss the numerous and interrelated changes in industrialized societies that have contributed to the epidemics of sexually transmitted diseases.

Antibiotic susceptibilities and auxotypes of Neisseria gonorrhoeae strains from women with pelvic inflammatory disease or uncomplicated infections.

The purpose of the present study was to compare the auxotypes and the minimal inhibitory concentrations of four antibiotics for 50 isolates from women with gonococcal pelvic inflammatory disease with those of 55 isolates from uncomplicated anogenital gonococcal infections. No significant differences in auxotype patterns and susceptibilities were found between isolates from the two groups.

Cefotaxime treatment of pelvic inflammatory disease.

We studied cefotaxime in the treatment of gonococcal and nongonococcal pelvic inflammatory disease. Cefotaxime was uniformly effective against gonococcal pelvic inflammatory disease. However, 4 of 11 patients with nongonococcal pelvic inflammatory disease had a suboptimal response.