Claire E. Stevens

A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection.

Abstract Background. Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors. Methods. We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. Results. Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA. The risk was highest among those with HPV type 16 or 18 infe...

Diagnosis and clinical manifestations of bacterial vaginosis

Among 640 randomly selected women who were attending a sexually transmitted disease clinic and did not have trichomoniasis, 33% had bacterial vaginosis as defined by a composite of four clinical criteria: (1) Vaginal discharge was homogeneous; (2) vaginal discharge had a pH greater than or equal to 4.7; (3) vaginal discharge had an amine-like odor when mixed with 10% potassium hydroxide; (4) vaginal discharge contained clue cells representing greater than or equal to 20% of vaginal epithelial cells. Previously published Gram stain criteria for bacterial vaginosis correlated better than results of semiquantitative cultures for Gardnerella vaginalis with presence or absence of clue cells and with composite clinical criteria. Of 293 women with bacterial vaginosis by Gram stain criteria, 65% had symptoms of increased vaginal discharge and/or vaginal malodor, while 74% had signs of characteristic homogeneous vaginal discharge or amine-like odor. Elevated vaginal pH was the least specific and amine-like odor the least sensitive sign of bacterial vaginosis. Gram stain criteria for bacterial vaginosis were not associated with the concentrations of endocervical or vaginal inflammatory cells but were significantly associated with a clinical diagnosis of pelvic inflammatory disease. After adjusting for coinfection, sexual behavior, and other variables, bacterial vaginosis remained associated with adnexal tenderness (odds ratio = 9.2, p = 0.04). Bacterial vaginosis, previously implicated as a risk factor for obstetric infections, may be a risk factor for pelvic inflammatory disease.

Mucopurulent cervicitis--the ignored counterpart in women of urethritis in men.

Among 100 randomly selected nonmenstruating women attending a clinic for sexually transmitted diseases, we assessed objective criteria for the clinical diagnosis of mucopurulent cervicitis. Visualization of yellow mucopurulent endocervical secretions on a white swab and the presence of 10 or more polymorphonuclear leukocytes per microscopical field (at a magnification of 1000) in satisfactory gram-stained endocervical smears were independently correlated with cervical Chlamydia trachomatis infection. Neither finding correlated with gonorrhea or genital herpes, although herpes caused characteristic cervical ulcerations. C. trachomatis was isolated from the cervix of 20 of 40 women with mucopurulent cervicitis but of only 2 of 60 without it. The overall prevalence of mucopurulent cervicitis among women attending the clinic (40 per cent) exceeded that of nongonococcal urethritis among men in the same clinic, and the prevalence of C. trachomatis infection was higher in mucopurulent cervicitis than in nongonococcal urethritis, a condition that is conventionally treated with tetracyclines. These findings support recommendations for the treatment of mucopurulent cervicitis and should guide the selective use of confirmatory diagnostic tests for C. trachomatis infection.

Mucopurulent Cervicitis and Mycoplasma genitalium

Many cases of mucopurulent cervicitis (MPC) are idiopathic and cannot be attributed to the known cervical pathogens Neisseria gonorrhoeae, Chlamydia trachomatis, or herpes simplex virus. Because Mycoplasma genitalium is associated with nongonoccocal urethritis in men, its role in MPC, the corresponding syndrome in women, was investigated. Archived cervical specimens from women recruited in the Harborview Sexually Transmitted Disease Clinic in Seattle from 1984 to 1986 were tested, using polymerase chain reaction, in a study that identified other causes of and risk factors for MPC. M. genitalium was detected in 50 (7.0%) of 719 women. Young age, multiple recent partners, prior miscarriage, smoking, menstrual cycle, and douching were positively associated with M. genitalium, whereas bacterial vaginosis and cunnilingus were negatively associated. After adjustment for age, phase of menstrual cycle, and presence of known cervical pathogens, women with M. genitalium had a 3.3-fold greater risk (95% confidence interval, 1.7-6.4) of MPC, which suggests that this organism may be a cause of MPC.

Vulvovaginal candidiasis : Clinical manifestations, risk factors, management algorithm

Objective To correlate symptoms, signs, and risk factors with positive wet mounts or cultures for Candida albicans and to develop an algorithm to diagnose vulvovaginal candidiasis. Methods This cross-sectional study of 774 randomly selected women from an urban sexually transmitted disease (STD) clinic evaluated symptoms, signs, and risk factors associated with C albicans, detected by wet mount and culture, and constructed an algorithm. Results C albicans, recovered from 186 (24%) of the 774 women, was associated with chief complaints of vulvar pruritus or burning. Elicited symptoms were vulvar pruritus, pain or burning, and external dysuria; signs were vulvar erythema, edema, fissures, vaginal erythema, and thick, curdy vaginal discharge. Among 545 women with symptoms of either increased vaginal discharge or vulvar pruritus or burning, only 155 (28%) had positive C albicans cultures, whereas bacterial vaginosis or other sexually transmitted infections were found in 288 (53%). In multivariate analysis, risk factors for positive C albicans culture included condom use, presentation after the 14th menstrual cycle day, sexual intercourse more than four times per month, recent antibiotic use, young age, past gonococcal infection, and absence of current gonorrhea or bacterial vaginosis. A clinical algorithm based on symptoms, signs, and selective use of wet mounts and cultures would have provided prompt treatment to 150 of 167 (90%) women with vulvovaginal candidiasis while minimizing the number of cultures performed. Conclusion A simple algorithm using symptoms, signs, wet mounts, and selective cultures can identify 90% of women with vulvovaginal candidiasis. In this STD clinic, vulvovaginal symptoms also require assessment for bacterial vaginosis, trichomoniasis, and cervical infection.

Determinants of cervical ectopia and of cervicitis: Age, oral contraception, specific cervical infection, smoking, and douching

OBJECTIVE Our purpose was to assess determinants of cervical ectopia and cervicitis, specifically after adjustment for cervical infection. STUDY DESIGN A cross-sectional study was conducted with colposcopic, cytologic, and microbiologic examination of 764 randomly selected women attending a sexually transmitted disease clinic and 819 consecutive college students undergoing routine annual examination. RESULTS After we controlled for potential confounders, cervical ectopia was positively associated with oral contraception and Chlamydia trachomatis infection and negatively associated with aging in both populations, with recent vaginal douching in patients with sexually transmitted diseases, and with current smoking in college students. Oral contraception wa also associated with the radius of ectopia, and among users of oral contraception ectopia was associated with duration of oral contraception. Cervicitis (evaluated by Gram stain, Papanicoloau smear, and colposcopy) was associated with cervical infection by C. trachomatis and cytomegalovirus (both populations) and with gonorrhea and cervical herpes simplex virus infection (patients with sexually transmitted diseases). Cervicitis was independently associated with ectopia but not with oral contraception after we adjusted for these four cervical infections. However, oral contraception was associated with edema and erythema of the zone of ectopia among women without cervical infection. CONCLUSIONS Oral contraception, aging, cervical infection, smoking, and douching have effects on cervical ectopia that may influence the acquisition, transmission, or effects of sexually transmitted agents. Ectopia is associated with young age, oral contraception, and cervical infection; cervicitis is associated with ectopia and cervical infection by C. trachomatis, Neisseria gonorrhoeae, herpes simplex virus, and cytomegalovirus. In women without cervical infection, edema and erythema of the zone of ectopia are associated with oral contraception.

The frequency of unrecognized type 2 herpes simplex virus infection among women : implications for the control of genital herpes

To evaluate the prevalence of symptomatic versus asymptomatic or unrecognized type 2 herpes simplex virus (HSV-2) infection, the authors performed physical examination, viral cultures, and type-specific serologic assays in 776 randomly selected women attending an STD clinic and 636 female university students. Forty-six percent of women attending the STD clinic compared with 8.8% of the university students had serologic evidence of HSV-2 infection. Clinical or historical evidence of genital herpes was present in only 34% of the HSV-2 seropositive women attending the STD clinic and in 29% of the HSV-2 seropositive women attending the university clinic. Among women attending the STD clinic, the prevalence of recognized genital infection was more common among those with HSV-2 antibodies only versus those with HSV-1 and -2 antibodies (odds ratio = 2.39; 95% confidence interval = 1.30-4.37), suggesting that HSV-1 infection reduces the likelihood of recognizing HSV-2 infection. In view of the high proportion of seropositive individuals with unrecognized HSV-2 infection in both high and low prevalence HSV-2 seropositive populations, newly developed HSV type-specific serologic methods should be evaluated for detecting carriers of HSV-2 infection and counseling these individuals about strategies for avoiding sexual and perinatal transmission of HSV-2.

Prevalence and manifestations of endometritis among women with cervicitis.

Thirty-five women referred from a clinic treating sexually transmitted diseases, because of suspected cervicitis, were studied for the presence of endometritis by transcervical endometrial biopsies and cervical and endometrial cultures. Fourteen (40%) of the patients had histologic evidence of endometritis. Findings that significantly correlated with endometritis included a history of intermenstrual vaginal bleeding, the presence of Chlamydia trachomatis, Neisseria gonorrhoeae, or Streptococcus agalactiae in the cervix, and the presence of serum antibodies to C. trachomatis or to Mycoplasma hominis.

Selection on the human immunodeficiency virus type 1 proteome following primary infection.

ABSTRACT Typically during human immunodeficiency virus type 1 (HIV-1) infection, a nearly homogeneous viral population first emerges and then diversifies over time due to selective forces that are poorly understood. To identify these forces, we conducted an intensive longitudinal study of viral genetic changes and T-cell immunity in one subject at ≤17 time points during his first 3 years of infection, and in his infecting partner near the time of transmission. Autologous peptides covering amino acid sites inferred to be under positive selection were powerful for identifying HIV-1-specific cytotoxic-T-lymphocyte (CTL) epitopes. Positive selection and mutations resulting in escape from CTLs occurred across the viral proteome. We detected 25 CTL epitopes, including 14 previously unreported. Seven new epitopes mapped to the viral Env protein, emphasizing Env as a major target of CTLs. One-third of the selected sites were associated with epitopic mutational escapes from CTLs. Most of these resulted from replacement with amino acids found at low database frequency. Another one-third represented acquisition of amino acids found at high database frequency, suggesting potential reversions of CTL epitopic sites recognized by the immune system of the transmitting partner and mutation toward improved viral fitness in the absence of immune targeting within the recipient. A majority of the remaining selected sites occurred in the envelope protein and may have been subjected to humoral immune selection. Hence, a majority of the amino acids undergoing selection in this subject appeared to result from fitness-balanced CTL selection, confirming CTLs as a dominant selective force in HIV-1 infection.

Prevalence and Correlates of Antibody to Chlamydial Heat Shock Protein in Women Attending Sexually Transmitted Disease Clinics and Women with Confirmed Pelvic Inflammatory Disease

A cross-sectional study of 306 women was done to correlate antibody to the chlamydial hsp60 (Chsp60) with epidemiologic, serologic, and laparoscopic findings of women with and without pelvic inflammatory disease (PID). Of the 306 women, 150 had confirmed PID by laparoscopic (n = 69) or histologic (n = 81) criteria, and 156 sexually transmitted disease clinic attendees without clinical PID did (n = 94) or did not (n = 62) have chlamydia. In multivariate analyses, Chsp60 antibody was independently associated with confirmed PID, age > 20 years, nonwhite race, > 10 lifetime sex partners, current oral contraceptive use, and IgG antibody titers; it was not associated with a positive Chlamydia trachomatis culture. Among the 69 women with laparoscopic evidence of PID, the highest level of Chsp60 antibody (optical density > 1.0) was found in 8 (80%) of 10 women with occluded tubes, compared with 11 (19%) of 58 with patent tubes (P < .001). We conclude that antibody to Chsp60 was significantly correlated with risk factors for PID, confirmed PID, and occluded fallopian tubes but not with acute C. trachomatis infection without PID.