Antonio J. Amortegui

Lower genital tract infection and endometritis: Insight into Subclinical pelvic inflammatory disease

OBJECTIVE To investigate the association between lower genital tract infections and subclinical PID. Fallopian tube damage is a common complication of acute symptomatic pelvic inflammatory disease (PID), yet most women with tubal factor infertility do not have a history of acute PID. Subclinical PID is believed to be an important cause of tubal factor infertility. METHODS We conducted a cross‐sectional study among women attending a sexually transmitted diseases or ambulatory gynecology clinic. A convenience sample of 556 women with bacterial vaginosis, gonorrhea, or chlamydia, or women at risk for gonorrhea or chlamydia were enrolled. Women diagnosed with acute PID were not eligible to participate. The main outcome was subclinical PID, as defined by the presence of histologic endometritis. RESULTS Subclinical PID was more common in women with lower genital tract infection than in uninfected women. Subclinical PID was present in 27% of women with Chlamydia trachomatis (odds ratio 3.4; 95% confidence interval [CI] 1.8, 6.3) and in 26% of women infected with Neisseria gonorrhoeae (odds ratio 2.4; 95% CI 1.1, 5.1). Among women with bacterial vaginosis, 15% had endometritis (odds ratio 2.7; 95% CI 1.02, 7.2). CONCLUSION Subclinical PID is common among women with lower genital tract infections. Additional prospective studies are necessary to determine the reproductive impact of these asymptomatic upper genital tract infections.

Douching and endometritis: results from the PID evaluation and clinical health (PEACH) study.

Background Douching has been related to risk of pelvic inflammatory disease (PID). Goal To examine the association between douching and PID in a large, multicenter, clinical trial of PID after adjustment for race/ethnicity. Study Design Interviews were conducted with 654 women who had signs and symptoms of PID. Vaginal Gram stains and upper genital tract pathology/cultures were obtained from all the women. Women with evidence of plasma cell endometritis and/or gonococcal or chlamydial upper genital tract infections were compared with women who had neither endometritis nor upper genital tract infection. Results Women with endometritis or upper genital tract infection were more likely to have douched more than once a month or within 6 days of enrollment than women who never douched. These associations remained after adjustment for confounding factors, after analysis of black women only; and among women with normal or intermediate vaginal flora but not bacterial vaginosis. Conclusion Among a predominantly black group of women with clinical PID, frequent and recent douching was associated with endometritis and upper genital tract infection.

Subclinical pelvic inflammatory disease and infertility.

OBJECTIVE: The reported incidence of acute pelvic inflammatory disease (PID) has decreased but rates of tubal infertility have not, suggesting that a large proportion of PID leading to infertility may be undetected. Subclinical PID is common in women with uncomplicated chlamydial or gonococcal cervicitis or with bacterial vaginosis. We assessed whether women with subclinical PID are at an increased risk for infertility. METHODS: A prospective observational cohort of 418 women with or at risk for gonorrhea or chlamydia or with bacterial vaginosis was recruited. Women with acute PID were excluded. An endometrial biopsy was performed to identify endometritis (subclinical PID). After provision of therapy for gonorrhea, chlamydia and bacterial vaginosis participants were followed-up for fertility outcomes. RESULTS: There were 146 incident pregnancies during follow-up, 50 pregnancies in 120 (42%) women with subclinical PID and 96 in 187 (51%) women without subclinical PID. Women with subclinical PID diagnosed at enrollment had a 40% reduced incidence of pregnancy compared with women without subclinical PID (hazard ratio 0.6, 95% confidence interval 0.4–0.8). Women with Neisseria gonorrhoeae or Chlamydia trachomatis, in the absence of subclinical PID, were not at increased risk for infertility. CONCLUSION: Subclinical PID decreases subsequent fertility despite provision of treatment for sexually transmitted diseases. These findings suggest that a proportion of female infertility is attributable to subclinical PID and indicate that current therapies for sexually transmitted diseases are inadequate for prevention of infertility. LEVEL OF EVIDENCE: II

Limitations of the criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease research

While endometrial neutrophils and plasma cells are criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease (PID) research, plasma cell misidentification and nonspecificity may limit the accuracy of these criteria. Herein, we examined: (1) the identification of endometrial plasma cells with conventional methyl green pyronin-based methodology versus plasma cell-specific (CD138) immunostaining, (2) the prevalence of endometrial plasma cells among women at low risk for PID, and (3) endometrial leukocyte subpopulations among women diagnosed with acute or chronic histologic endometritis by conventional criteria. We observed an absence of CD138+ cells in 25% of endometrial biopsies in which plasma cells had been identified by conventional methodology, while additional immunohistochemical analyses revealed indistinguishable inflammatory infiltrates among women diagnosed with acute or chronic endometritis by conventional criteria. Among women considered at lower risk for PID development, flow cytometric analyses detected plasma cells in 30% of endometrial biopsy specimens, suggesting that these cells, even when accurately identified, only nonspecifically identify upper genital tract inflammatory processes. Combined, our findings underscore the limitations of the criteria used to diagnose histologic endometritis in PID-related research and suggest that satisfactory understanding of PID pathogenesis, treatment, and prevention is hindered by continued use of these criteria.

Endometrial plasma cells: do they indicate subclinical pelvic inflammatory disease?

Background: Subclinical pelvic inflammatory disease (PID) is a common condition among women with lower genital tract infection and is believed to be responsible for a greater proportion of PID-related sequelae than acute PID. Subclinical PID is diagnosed histologically after endometrial biopsy. In the literature, many different histologic criteria have been used to define subclinical PID. Goal: To determine if endometrial plasma cells are commonly found in women at low likelihood of PID. Study: A cross-sectional study of 33 women undergoing tubal ligation and at low likelihood of PID was performed. At the time of tubal ligation, study participants underwent visualization of pelvic organs and an endometrial biopsy, which was analyzed for the presence of neutrophils and plasma cells. Demographic, clinical, and microbiologic data were compared among women with and without endometrial plasma cells. Results: Endometrial plasma cells were identified in one third (33%) of the asymptomatic, fertile, healthy women in our cohort. The presence of plasma cells was not associated with lower genital tract infection, including bacterial vaginosis. Laparoscopic evidence of fallopian tube damage was similar in patients with and without endometrial plasma cells (22% in each group). Conclusion: Plasma cells are commonly found in the endometria of healthy women and may not represent upper genital tract inflammation.

Immunodiagnosis of Adult Chlamydial Conjunctivitis

This study presents data from a prospective comparison of four currently available diagnostic tests for Chlamydia trachomatis infection. Seventy-six patients clinically suspicious for chlamydial conjunctivitis were all tested with Giemsa stain cytology, direct monoclonal fluorescent antibody (DFA) microscopy, enzyme immunosorbent assay (EIA) for chlamydial antigens, and standard McCoy cell culture. When compared with primary cell culture, diagnostic Giemsa inclusions had a sensitivity and specificity of 43 and 100%, respectively, supportive Giemsa cytology 71 and 67%, the enzyme immunoassay 71 and 97%, and the monoclonal fluorescent antibody 57 and 81%. Each nonculture method has distinct advantages in terms of cost, technical difficulty, speed, and accuracy, which dictate selection of the most appropriate test for office or laboratory diagnosis of chlamydial conjunctivitis.

Detection of human papillomavirus DNA in cervical lesions by in situ hybridization using biotinylated DNA probes

In situ hybridization (ISH) for human papillomavirus (HPV)-6, -11, -16, -18, and -31 DNA was performed on 615 formalin-fixed paraffin-embedded cervical biopsies using biotinylated DNA probes. Results were obtained from 584 samples with 266 (45.5%) containing HPV-DNA sequences. Ninety percent of condyloma acuminatum specimens were positive for HPV-DNA with 18 of 19 positive cases containing HPV-6 or -11 DNA. The detection rate of HPV in cervical intraepithelial neoplasia (CIN) lesions was 50.6% (239 of 472), while only 8 of 91 (8.9%) cervical biopsies considered to be histologically normal or with minimal dysplasia contained HPV-DNA as demonstrated by ISH. The prevalence of HPV-16, -18, and/or -31 DNA increased with the severity of the lesions, with 20 of 20 (100%) positive CIN-III lesions containing these viral types compared with 102 of 157 (65.0%) positive CIN-I lesions. ISH with biotinylated DNA probes appears helpful in identifying lesions containing higher risk viral strains.

In-situ hybridization for the diagnosis and typing of human papillomavirus

The human papillomavirus (HPV) has been associated with the production of many skin and mucosal lesions, the development of squamous cell carcinoma of the genital areas, skin and aerodigestive tracts, and possibly adenocarcinoma of the uterine cervix. There are more than 60 known genotypes of HPV. Some genotypes have been associated with lesions that have none or minimal chances of malignant transformation; while other genotypes (especially types 16, 18, 31, 35, and 51) have been found in mild, moderate, and severe dysplasia, carcinoma in-situ or frank invasive carcinoma. HPV cannot be propagated in tissue cultures. The presence of the virus can be demonstrated by immunologic techniques, which are not sensitive enough with the present methodology, or by searching for the presence of the viral DNA by DNA or RNA hybridization techniques. Determining the viral genotype in the tissue involved will permit the separation of those lesions supposedly to be low risk from those associated with the high risk types. This knowledge may be helpful in the future to determine the appropriate management of patients infected with HPV.

Changes in the frequency of genital herpes recurrences as a function of time.

To obtain objective information regarding changes in the frequency of recurrent genital Herpes simplex infections, the data from two consecutive pregnancies in 22 women with culture-proved genital Herpes simplex infections were reviewed. The pregnancies studied were separated by a mean of 2.0 years. When only culture-proved recurrences were considered, nine women had fewer recurrences in their second pregnancy than in their first, four had more recurrences in their second than in their first, and nine had the same number of recurrences in both pregnancies. The mean interval between culture-proved recurrences was 58.5 +/- 36.1 (SD) days in first pregnancies and 51.7 +/- 28.6 days in second pregnancies. Mean duration of viral shedding during 14 recurrences in first pregnancies was 4.6 +/- 3.4 days, and 3.2 +/- 2.2 days in 14 recurrences in second pregnancies (differences not significant by Mann-Whitney). Cervical Herpes simplex shedding in asymptomatic women occurred in four of 200 (2.0%) of first pregnancy cultures and zero of 167 second pregnancy cultures (NS). During culture-positive recurrent vulvar infections, 18 of 55 (32.7%) cervical cultures in first pregnancies were positive compared with four of 50 (8%) cervical cultures in second pregnancies (P less than .025). Route of delivery was very similar in the first and second pregnancies with vaginal delivery in 63.6% of first pregnancies and 72.7% of second pregnancies. Overall there was no appreciable difference in the frequency or severity of recurrent genital Herpes simplex infections over time, but more data are needed.

The effect of chemical intravaginal contraceptives and Betadine on Ureaplasma urealyticum

The purpose of this study was to find a barrier contraceptive agent capable of controlling infections and sexual transmission of Ureaplasma urealyticum from the female genital tract, especially to help reduce nongonococcal urethritis in males caused by this organism. Therefore, the in vitro antimicrobial activity of six intravaginal contraceptives and BetadineR against the eight serotypes of the organism was investigated. The results indicate that some of these contraceptives produce partial inhibition of the Ureaplasma at low dilutions, while BetadineR produces a ureaplasmacidal effect up to dilutions of 1:64. These effects appear not to be due primarily to the pH of these agents. Thus, some of these agents may have a potential role in controlling transmission of Ureaplasma urealyticum.