David A. Eschenbach

Nonspecific vaginitis: Diagnostic criteria and microbial and epidemiologic associations☆

Numerous previous studies of nonspecific vaginitis have yielded contradictory results regarding its cause and clinical manifestations, due to a lack of uniform case definition and laboratory methods. We studied 397 consecutive unselected female university students and applied sets of well defined criteria to distinguish nonspecific vaginitis from other forms of vaginitis and from normal findings. Using such criteria, we diagnosed nonspecific vaginitis in up to 25 percent of our study population; asymptomatic disease was recognized in more than 50 percent of those with nonspecific vaginitis. A clinical diagnosis of nonspecific vaginitis, based on simple office procedures, was correlated with both the presence and the concentration of Gardnerella vaginalis (Hemophilus vaginalis) in vaginal discharge, and with characteristic biochemical findings in vaginal discharge. Nonspecific vaginitis was also correlated with a history of sexual activity, a history of previous trichomoniasis, current use of nonbarrier contraceptive methods, and, particularly, use of an intrauterine device. G. vaginalis was isolated from 51.3 percent of the total population using a highly selective medium that detected the organism in lower concentration in vaginal discharge than did previously used media. Practical diagnostic criteria for standard clinical use are proposed. Application of such criteria should assist in clinical management of nonspecific vaginitis and in further study of the microbiologic and biochemical correlates and the pathogenesis of this mild but quite prevalent disease.

Trichomonas vaginalis associated with Low birth weight and preterm delivery

Background: Several studies have suggested that pregnant women infected with Trichomonas vaginalis may be at increased risk of an adverse outcome. Goal: To evaluate prospectively the association between T. vaginalis and risk of adverse pregnancy outcome in a large cohort of ethnically diverse women. Study Design: At University‐affiliated hospitals and antepartum clinics in five United States cities, 13,816 women (5,241 black, 4,226 Hispanic, and 4,349 white women) were enrolled at mid‐gestation, tested for T. vaginalis by culture, and followed up until delivery. Results: The prevalence of T. vaginalis infection at enrollment was 12.6%. Race‐specific prevalence rates were 22.8% for black, 6.6% for Hispanic, and 6.1% for white women. After multivariate analysis, vaginal infection with T. vaginalis at mid‐gestation was significantly associated with low birth weight (odds ratio 1.3; 95% confidence interval 1.1 to 1.5), preterm delivery (odds ratio 1.3; 95% confidence interval 1.1 to 1.4), and preterm delivery of a low birth weight infant (odds ratio 1.4; 95% confidence interval 1.1 to 1.6). The attributable risk of T. vaginalis infection associated with low birth weight in blacks was 11% compared with 1.6% in Hispanics and 1.5% in whites. Conclusions: After considering other recognized risk factors including co‐infections, pregnant women infected with T. vaginalis at mid‐gestation were statistically significantly more likely to have a low birth weight infant, to deliver preterm, and to have a preterm low birth weight infant. Compared with whites and Hispanics, T. vaginalis infection accounts for a disproportionately larger share of the low birth weight rate in blacks.

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.

Initial Events in Establishing Vaginal Entry and Infection by Human Immunodeficiency Virus Type-1

Summary Understanding the initial events in the establishment of vaginal human immunodeficiency virus type-1 (HIV-1) entry and infection has been hampered by the lack of appropriate experimental models. Here, we show in an ex vivo human organ culture system that upon contact in situ, HIV-1 rapidly penetrated both intraepithelial vaginal Langerhans and CD4+ T cells. HIV-1 entered CD4+ T cells almost exclusively by CD4 and CCR5 receptor-mediated direct fusion, without requiring passage from Langerhans cells, and overt productive infection ensued. By contrast, HIV-1 entered CD1a+ Langerhans cells primarily by endocytosis, by means of multiple receptors, and virions persisted intact within the cytoplasm for several days. Our findings shed light on the very earliest steps of mucosal HIV infection in vivo and may guide the design of effective strategies to block local transmission and prevent HIV-1 spread.

Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis

Maternal genital infection, particularly subclinical amniotic fluid infection, may cause preterm labor and a premature delivery. The prevalence of subclinical amniotic fluid infection was studied in 54 consecutive afebrile women in preterm labor with singleton gestations and intact fetal membranes. Microorganisms were recovered from the amniotic fluid by transabdominal amniocentesis in 13 (24%) of 54 patients. Bacteria or Candida albicans were recovered from six (11%), and genital mycoplasmas from seven (13%). Compared with women with sterile amniotic fluid, patients whose amniotic fluid contained bacteria or Candida organisms had a shorter interval from onset of preterm labor until delivery (0.6 versus 34.3 days, P less than .01), were less responsive to tocolytic therapy (0 versus 81% success rate, P less than .005), and more frequently developed subsequent intrapartum fever (83 versus 2.4%, P less than .005). In contrast, women whose amniotic fluid contained genital mycoplasmas did not differ in these parameters from those with sterile fluid. Also compared was cervical-vaginal infection among these patients in preterm labor with matched control subjects without preterm labor. In this analysis, bacterial vaginosis was identified in 43% of patients with and 14% of women without preterm labor (P = .02), yielding a relative risk of preterm labor for patients with bacterial vaginosis of 3.8. These data underscore the importance of amniotic fluid bacterial infections in preterm labor and premature delivery, and suggest that bacterial vaginosis is associated with prematurity.

Polymicrobial etiology of acute pelvic inflammatory disease.

We studied 204 women with acute pelvic inflammatory disease to delineate further the causes of that illness. Gonococci were recovered from 91. Gonococcal pili antibody rose or fell significantly in 12 of 18 patients with positive cultures and only two of 19 who had negative cultures and smears for Neisseria gonorrhaoea(P smaller than 0.005). N. gonorrhoeae was found in peritoneal exudate from eight of 21 patients with, and none of 33 without, cervical gonococcal infection. Among patients with severe disease, other bacteria were recovered from peritoneal exudates from five of 16 with, and 19 of 22 without, cervical gonococcal infection (P smaller than 0.025). Mixed anaerobic and aerobic bacterial peritoneal infection was common in nongonococcal pelvic disease. The most common species recovered were Bacteroides fragilis, peptostreptococci, and peptococci. Tuboperitoneal gonococcal infection probably causes pelvic inflammatory disease in most patients with cervical gonococcal infection, whereas polymicrobial tuboperitoneal infection probably causes most nongonococcal cases.

Anaerobic Bacteria in Nonspecific Vaginitis

To study the cause of nonspecific vaginitis, we analyzed vaginal fluid from normal women and from 53 women with nonspecific vaginitis, using quantitative anaerobic cultures and gas-liquid chromatography for short-chained organic-acid metabolites of the microbial flora. In normal vaginal fluid, lactate was the predominant acid, and the predominant organisms were lactobacillus and streptococcus species (lactate producers). In nonspecific vaginitis, lactate was decreased, whereas succinate, acetate, butyrate, and propionate were increased, the predominant flora included Gardnerella (Haemophilus) vaginalis (acetate producer), and anaerobes, which included bacteroides species (succinate producers) and peptococcus species (butyrate and acetate producers). After metronidazole therapy, symptoms and signs of nonspecific vaginitis cleared, butyrate and propionate disappeared, and lactate and lactate-producing organisms became predominant. We conclude that certain anaerobes act with G. vaginalis as causes of nonspecific vaginitis, and that a high ratio of succinate to lactate in vaginal fluid is a useful indicator in the diagnosis of this condition.

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.

Characterization of Vaginal Flora and Bacterial Vaginosis in Women Who Have Sex with Women

Bacterial vaginosis (BV) may be common among women who report having sex with women (WSW) and frequently occurs in both members of monogamous couples. The results of Gram staining of a vaginal smear were consistent with BV in 81 (25%) and intermediate in 37 (11%) of 326 WSW included in this study. Lactobacilli were detected in 64% of subjects, and 42% of subjects had H(2)O(2)-producing strains. BV was associated with a higher lifetime number of female sex partners, failure to always clean an insertive sex toy before use, and oral-anal sex with female partners. Neither recent douching nor sexual practices with male partners were associated with BV. Vaginal smears from each partner were concordant in 55 (95%) of 58 monogamous couples; BV was present in both partners in 16 couples (28%) (P<.001, compared with expected distribution). BV was common among subjects who did not douche, who did not have concurrent sex with male partners, or who did not have a new sex partner, which suggests that other risk factors for BV exist. These data support the hypothesis that sexual exchange of vaginal secretions is a possible mechanism for acquisition of BV.

The relationship of hydrogen peroxide-producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women.

Lactobacilli provide an important microbial defense against genital colonization by pathogens. The role of hydrogen peroxide (H2O2) in the control of genital microflora was explored in a cross-sectional study of 275 women in the second trimester of pregnancy. Vaginal cultures were obtained for detec