Catherine L. Haggerty

Risk of sequelae after Chlamydia trachomatis genital infection in women.

Chlamydia trachomatis infection, the most common reportable disease in the United States, can lead to pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and chronic pelvic pain. Although C. trachomatis is identified among many women who receive a diagnosis of PID, the incidence and timing of PID and long-term sequelae from an untreated chlamydial infection have not been fully determined. This article examines evidence reviewed as part of the Centers for Disease Control and Prevention Chlamydia Immunology and Control Expert Advisory Meeting; 24 reports were included. We found no prospective studies directly assessing risk of long-term reproductive sequelae, such as infertility, after untreated C. trachomatis infection. Several studies assessed PID diagnosis after untreated chlamydial infection, but rates varied widely, making it difficult to determine an overall estimate. In high-risk settings, 2%-5% of untreated women developed PID within the approximately 2-week period between testing positive for C. trachomatis and returning for treatment. However, the rate of PID progression in the general, asymptomatic population followed up for longer periods appeared to be low. According to the largest studies, after symptomatic PID of any cause has occurred, up to 18% of women may develop infertility. In several studies, repeated chlamydial infection was associated with PID and other reproductive sequelae, although it was difficult to determine whether the risk per infection increased with each recurrent episode. The present review critically evaluates this body of literature and suggests future research directions. Specifically, prospective studies assessing rates of symptomatic PID, subclinical tubal damage, and long-term reproductive sequelae after C. trachomatis infection; better tools to measure PID and tubal damage; and studies on the natural history of repeated chlamydial infections are needed.

Strength and muscle quality in a well-functioning cohort of older adults: the Health, Aging and Body Composition Study.

OBJECTIVES:  To determine whether lower lean mass and higher fat mass have independent effects on the loss of strength and muscle quality in older adults and might explain part of the effect of age.

Bacterial Vaginosis and Anaerobic Bacteria Are Associated with Endometritis

BACKGROUND Chlamydia trachomatis and/or Neisseria gonorrhoeae account for approximately one-third to one-half of pelvic inflammatory disease (PID) cases. Thus, up to 70% of cases have an unknown, nongonococcal/nonchlamydial microbial etiology. METHODS We investigated the associations of N. gonorrhoeae, C. trachomatis, bacterial vaginosis, anaerobic bacteria, facultative bacteria, and lactobacilli with endometritis among 278 women with complete endometrial histology and culture from the PID Evaluation and Clinical Health Study. RESULTS Women with acute endometritis were less likely to have H(2)O(2)-producing Lactobacillus species (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.01-0.8) and more likely to be infected with C. trachomatis (OR, 16.2; 95% CI, 4.6-56.6), N. gonorrhoeae (OR, 11.6; 95% CI, 4.5-29.9), diphtheroids (OR, 5.0; 95% CI, 2.1-12.2), black-pigmented gram-negative rods (OR, 3.1; 95% CI, 1.4-7.0), and anaerobic gram-positive cocci (OR, 2.1; 95% CI, 1.0-4.3) and to have bacterial vaginosis (OR, 2.4; 95% CI, 1.3-4.3). CONCLUSIONS We conclude that bacterial vaginosis-associated organisms are frequent among women with PID. Because these organisms were strongly associated with endometritis, we recommend that all women with PID be treated with regimens that include metronidazole.

The impact of estrogen and progesterone on asthma.

OBJECTIVE This paper describes evidence of a positive effect of both endogenous and exogenous estrogen and progesterone on lung function across the life span in women. DATA SOURCES Articles were identified using the keywords asthma, pulmonary function, menarche, menopause, estrogen, progesterone, hormone replacement therapy, oral contraceptives, and menstrual cycle from years 1966 to 2001 in MEDLINE. Additional studies were identified from article reference lists. STUDY SELECTION Relevant, peer-reviewed original research articles in the English language were selected. RESULTS Estrogen and/or progesterone may alter pulmonary function and asthma. Premenopausal women experience decreases in pulmonary function and increases in asthma exacerbations and hospitalizations during the premenstrual and menstrual phases. Oral contraceptives and hormone replacement therapy are associated with improved pulmonary function and decrease in asthma exacerbation. Some asthmatic patients experience improved pulmonary function and reduced asthma medication requirement during pregnancy. CONCLUSIONS Estrogen and progesterone modify airway responsiveness. Further research is needed to elucidate the clinical relevance of estrogen and progesterone in the pathophysiology and therapy of asthma.

Failure of cefoxitin and doxycycline to eradicate endometrial Mycoplasma genitalium and the consequence for clinical cure of pelvic inflammatory disease

Objectives: As Mycoplasma genitalium is associated with pelvic inflammatory disease (PID), we examined the efficacy of a commonly used PID antimicrobial in treating M genitalium upper genital tract infection. Methods: In the PID Evaluation and Clinical Health study of inpatient versus outpatient treatment, 682 women treated with cefoxitin and doxycycline for clinically suspected PID had stored cervical and endometrial specimens available for analysis. In the current sub study, we compared baseline endometritis, short term treatment failure (continued endometritis and pelvic pain 30 days following treatment) and sequelae among women with and without M genitalium, identified using PCR. Results: Endometrial M genitalium was associated with baseline endometritis (adjusted OR 3.0, 95% CI 1.5 to 6.1). Among women with a positive baseline M genitalium test, 41% tested positive again 30 days following treatment. Women testing positive compared to those testing negative for M genitalium at baseline had an increased risk of short-term treatment failure (RR 4.6, 95% CI 1.1 to 20.1). Rates of sequelae, including infertility (22%), recurrent PID (31%) and chronic pelvic pain (42%), were high among women testing positive for endometrial M genitalium at baseline. There was a non-significant trend towards increased infertility, chronic pelvic pain and recurrent PID, and decreased pregnancy and live birth following M genitalium infection. Conclusions: M genitalium is associated with endometritis and short-term PID treatment failure. Cefoxitin and doxycycline, a Centers for Disease Control and Prevention recommended PID treatment regimen, is ineffective for the treatment of M genitalium upper genital tract infection.

Evidence for a role of Mycoplasma genitalium in pelvic inflammatory disease.

Purpose of review Mycoplasma genitalium is a common sexually transmitted pathogen frequently identified among women with pelvic inflammatory disease, the infection and inflammation of a womans upper genital tract. Although Chlamydia trachomatis and Neisseria gonorrhoeae frequently cause pelvic inflammatory disease, up to 70% of cases have unidentified etiology. This review summarizes recent evidence for M. genitaliums role in pelvic inflammatory disease and subsequent sequelae. Recent findings PCR studies have demonstrated that M. genitalium is associated with clinically suspected pelvic inflammatory disease, acute endometritis, and adnexitis, independent of gonococcal and chlamydial infection. Most studies have been cross-sectional, although one prospective investigation suggested that M. genitalium was associated with over a 13-fold risk of endometritis. Whether or not M. genitalium upper-genital-tract infection results in reproductive morbidity is unclear, although it has been serologically associated with tubal-factor infertility. Several lines of evidence suggest that M. genitalium is likely resistant to many frequently used pelvic inflammatory disease treatments. Correspondingly, M. genitalium has been associated with treatment failure following cefoxitin and doxycycline treatment for clinically suspected pelvic inflammatory disease. Summary Strong evidence suggests that M. genitalium is associated with pelvic inflammatory disease. Further study of M. genitalium upper-genital-tract infection diagnosis and treatment is warranted.

Clinical presentation of Mycoplasma genitalium infection versus Neisseria gonorrhoeae infection among women with pelvic inflammatory disease.

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Mycoplasma genitalium among women with nongonococcal, nonchlamydial pelvic inflammatory disease.

Pelvic inflammatory disease (PID) is a frequent condition of young women, often resulting in reproductive morbidity. Although Neisseria gonorrhoeae and/or Chlamydia trachomatis are/is recovered from approximately a third to a half of women with PID, the etiologic agent is often unidentified. We need PCR to test for M genitalium among a pilot sample of 50 women with nongonococcal, nonchlamydial endometritis enrolled in the PID evaluation and clinical health (PEACH) study. All participants had pelvic pain, pelvic organ tenderness, and leukorrhea, mucopurulent cervicitis, or untreated cervicitis. Endometritis was defined as ≥5 surface epithelium neutrophils per ×400 field absent of menstrual endometrium and/or ≥2 stromal plasma cells per ×120 field. We detected M genitalium in 7 (14%) of the women tested: 6 (12%) in cervical specimens and 4 (8%) in endometrial specimens. We conclude that M genitalium is prevalent in the endometrium of women with nongonococcal, nonchlamydial PID.

Chlamydia trachomatis-infected patients display variable antibody profiles against the nine-member polymorphic membrane protein family.

ABSTRACT Genomic analysis of the Chlamydiaceae has revealed a multigene family encoding large, putatively autotransported polymorphic membrane proteins (Pmps) with nine members in the sexually transmitted pathogen Chlamydia trachomatis. While various pathogenesis-related functions are emerging for the Pmps, observed genotypic and phenotypic variation among several chlamydial Pmps in various Chlamydia species has led us to hypothesize that the pmp gene repertoire is the basis of a previously undetected mechanism of antigenic variation. To test this hypothesis, we chose to examine the serologic response of C. trachomatis-infected patients to each Pmp subtype. Immune serum samples were collected from four populations of patients with confirmed C. trachomatis genital infection: 40 women with pelvic inflammatory disease from Pittsburgh, PA; 27 and 34 adolescent/young females from Oakland, CA, and Little Rock, AR, respectively; and 58 adult male patients from Baltimore, MD. The Pmp-specific antibody response was obtained using immunoblot analysis against each of the nine recombinantly expressed Pmps and quantified by densitometry. Our results show that nearly all C. trachomatis-infected patients mount a strong serologic response against individual or multiple Pmp subtypes and that the antibody specificity profile varies between patients. Moreover, our analysis reveals differences in the strengths and specificities of the Pmp subtype-specific antibody reactivity relating to gender and clinical outcome. Overall, our results indicate that the Pmps elicit various serologic responses in C. trachomatis-infected patients and are consistent with the pmp gene family being the basis of a mechanism of antigenic variation.

Clinical characteristics of bacterial vaginosis among women testing positive for fastidious bacteria.

Objectives: As the aetiology of bacterial vaginosis (BV) is not well understood, this study sought to determine the relationships between several fastidious microbes, BV and selected clinical characteristics of BV. Methods: Endometrial and cervical specimens from 50 women with non-gonococcal, non-chlamydial endometritis were tested for Leptotrichia sanguinegens/amnionii, Atopobium vaginae, bacterial vaginosis-associated bacteria 1 (BVAB1), Ureaplasma urealyticum biovar 2 (UU-2) and Ureaplasma parvum using PCR. BV was categorised using Nugent’s and Amsel’s criteria. Odds ratios (OR) adjusted for age and race were estimated using multivariable logistic regression. Results: Although elevated pH was a universal feature, other BV characteristics differed by pathogen, suggesting variable clinical presentation. Only UU-2 was strongly associated with vaginal discharge, but a positive whiff test and a 20% or greater classification of epithelial cells as clue cells were more common among women with L sanguinegens/amnionii, A vaginae and BVAB1. For each of these bacteria, there were trends towards associations with BV defined by Amsel’s criteria (L sanguinegens/amnionii OR 2.9, 95% CI 0.5 to 15.7; A vaginae OR 2.6, 95% CI 0.6 to 11.4; BVAB1 OR 5.7, 95% CI 1.0 to 31.1) and significant associations with BV defined by Gram stain (L sanguinegens/amnionii OR 17.7, 95% CI 2.8 to 113.0; A vaginae OR 19.2, 95% CI 3.7 to 98.7; BVAB1 OR 21.1, 95% CI 2.2 to 198.5). Conclusions: L sanguinegens/amnionii, A vaginae and BVAB1 are associated with clinical characteristics consistent with BV and BV defined by Nugent’s and Amsel’s criteria. These fastidious bacteria may cause unrecognised infection, as none was associated with abnormal vaginal discharge.