Jane R. Schwebke

Validity of the vaginal gram stain for the diagnosis of bacterial vaginosis

Objective To determine the sensitivity and specificity of vaginal Gram stain as interpreted by the Nugent criteria for the diagnosis of bacterial vaginosis, and to consider the use of Gram stain as the criterion standard for the diagnosis of bacterial vaginosis. Methods A multicenter study was conducted of women attending gynecology or sexually transmitted disease clinics. Clinical data consisting of vaginal pH, “whiff test,” clue cells, and appearance of the vaginal discharge (Amsel criteria) were compared with the vaginal fluid Gram stain (Nugent criteria) for the diagnosis of bacterial vaginosis. Results The sensitivity and specificity of the Gram stain compared with the Amsel criteria were 89 and 83%, respectively. There was significant variation in the specificity values by geographic site. If the Gram stain was considered the criterion standard for the diagnosis of bacterial vaginosis, the sensitivity and specificity of the Amsel criteria were 70 and 94%, respectively. Conclusion The vaginal Gram stain (Nugent criteria) is a sensitive method for the diagnosis of bacterial vaginosis. The 83% specificity suggests that the currently used Amsel criteria may lead to the underdiagnosis of bacterial vaginosis.

Bacterial Vaginosis Assessed by Gram Stain and Diminished Colonization Resistance to Incident Gonococcal, Chlamydial, and Trichomonal Genital Infection

BACKGROUND We sought to assess the relationship between bacterial vaginosis (BV) assessed by Gram stain and incident trichomonal, gonococcal, and/or chlamydial genital infection. METHODS This longitudinal study included 3620 nonpregnant women aged 15-44 years who presented for routine care at 12 clinics in Birmingham, Alabama. Participants were assessed quarterly for 1 year. Vaginal smears were categorized by the Nugent Gram stain score (0-3, normal; 4-6, intermediate state; 7-10, BV). Pooled logistic regression was used to estimate the hazard ratios for the comparison of trichomonal, gonococcal, and chlamydial infection incidence in participants by Nugent score at the prior visit. Participants were censored at their first visit with a positive test result for trichomonal, gonococcal, and/or chlamydial infection. RESULTS Of the 10,606 eligible visits, 37.96% were classified by BV and 13.3% by positive detection of trichomonal, gonococcal, and/or chlamydial infection. An intermediate state or BV at the prior visit was associated with a 1.5-2-fold increased risk for incident trichomonal, gonococcal, and/or chlamydial infection (adjusted hazard ratio [AHR] for intermediate state, 1.41 [95% confidence interval {CI}, 1.12-1.76]; AHR for BV, 1.73 [95% CI, 1.42-2.11]; P= .058 for trend). Estimates were similar for trichomonal-only, gonococcal-only, and chlamydial-only infection outcomes. CONCLUSION BV microbiota as gauged by Gram stain is associated with a significantly elevated risk for acquisition of trichomonal, gonococcal, and/or chlamydial genital infection.

Re-Evaluating the Treatment of Nongonococcal Urethritis: Emphasizing Emerging Pathogens–A Randomized Clinical Trial

BACKGROUND Nongonococcal urethritis (NGU) is a common chlamydia-associated syndrome in men; however, Trichomonas vaginalis and Mycoplasma genitalium are associated with its etiology and should be considered in approaches to therapy. We sought to determine whether the addition of tinidazole, an anti-trichomonal agent, to the treatment regimen would result in higher cure rates than those achieved with treatment with doxycycline or azithromycin alone. A secondary aim was to compare the efficacy of doxycycline therapy and with that of azithromycin therapy. METHODS Randomized, controlled, double-blinded phase IIB trial of men with NGU. Participants were randomized to receive doxycycline plus or minus tinidazole or azithromycin plus or minus tinidazole and were observed for up to 45 days. RESULTS The prevalences of Chlamydia trachomatis, M. genitalium, and T. vaginalis were 43%, 31%, and 13%, respectively. No pathogens were identified in 29% of participants. Clinical cure rates at the first follow-up visit were 74.5% (111 of 149 patients) for doxycycline-containing regimens and 68.6% (107 of 156 patients) for azithromycin-containing regimens. By the final visit, cure rates were 49% (73 of 149 patients) for doxycycline-containing regimens and 43.6% (68 of 156 patients) for azithromycin-containing regimens. There were no significant differences in clinical response rates among the treatment arms. However, the chlamydia clearance rate was 94.8% (55 of 58 patients) for the doxycycline arm and 77.4% (41 of 53 patients) for the azithromycin arm (P = .011), and the M. genitalium clearance rate was 30.8% (12 of 39 patients) for the doxycycline arm and 66.7% (30 of 45 patients) for the azithromycin arm (P = .002). CONCLUSIONS Addition of tinidazole to the treatment regimen did not result in higher cure rates but effectively eradicated trichomonas. Clinical cure rates were not significantly different between patients treated with doxycycline and those treated with azithromycin; however, doxycycline had significantly better efficacy against Chlamydia, whereas azithromycin was superior to doxycycline for the treatment of M. genitalium.

Vulvovaginal symptoms in women with bacterial vaginosis.

OBJECTIVE: A substantial, but highly variable, percentage of women with bacterial vaginosis are said to be asymptomatic. The purpose of this study was to estimate the prevalence of symptoms among women with bacterial vaginosis compared with women without bacterial vaginosis by direct, explicit, and detailed questioning of these women. METHODS: Women presenting for a routine health care visit at 12 health department clinics in Birmingham, Alabama, were recruited to participate in a longitudinal study of vaginal flora. At the first visit, they underwent a pelvic examination, lower genital tract microbiological evaluation, and an interview that included detailed questions regarding lower genital tract symptoms. The prevalence of symptoms among women with and without bacterial vaginosis (Gram stain score 7 or higher) was compared. RESULTS: Among 2,888 women without gonorrhea, Chlamydia, or trichomonas, 75% of women with and 82% of women without bacterial vaginosis never noted any vaginal odor in the past 6 months (P < .001). The corresponding values were 63% and 65% for never noting vaginal “wetness” (P = .02); 58% and 57% for vaginal discharge (P = .65); 91% and 86% for irritation (P = .004); 88% and 85% for itching (P = .64); and 96% and 94% for dysuria (P = .002), respectively. Cumulatively, 58% of women with bacterial vaginosis noted odor, discharge, and/or wetness in the past 6 months compared with 57% of women without bacterial vaginosis (P = .70). CONCLUSION: The 2 classic symptoms of bacterial vaginosis discharge and odor are each reported by a minority of women with bacterial vaginosis and are only slightly more prevalent than among women without bacterial vaginosis. LEVEL OF EVIDENCE: II-3

Comparison of APTIMA Trichomonas vaginalis transcription-mediated amplification to wet mount microscopy, culture, and polymerase chain reaction for diagnosis of trichomoniasis in men and women

OBJECTIVE We evaluated the performance characteristics of APTIMA Trichomonas vaginalis (ATV) transcription-mediated amplification (TMA) for diagnosis of T vaginalis (TV) infection from female vaginal swab, endocervical swab, and urine specimens and from male urethral swab and urine specimens. Performance of ATV TMA was compared with wet mount microscopy, culture, and polymerase chain reaction (PCR). STUDY DESIGN In all, 296 female and 298 male subjects who attended the Jefferson County Health Department sexually transmitted diseases clinic were enrolled in the study and provided specimens for each test. Results were analyzed using 3 interpretative algorithms. RESULTS For women, vaginal swab ATV TMA was significantly more sensitive than wet mount or culture. In male subjects, urethral swab ATV TMA was significantly more sensitive than culture or PCR. CONCLUSION ATV TMA provides a sensitive, commercially available nucleic acid amplification test for improved diagnosis of TV in male and female patients.

A Randomized, Double-Blind, Placebo-Controlled Trial of Combined Nevirapine and Zidovudine Compared with Nevirapine Alone in the Prevention of Perinatal Transmission of HIV in Zimbabwe

Background. Trichomonas vaginalis causes a common sexually transmitted infection (STI) in women, yet trichomoniasis in male sexual partners is not well recognized. Nucleic acid amplification tests can increase detection of T. vaginalis in men compared with culture.Methods. We conducted a prospective, multicenter study to evaluate T. vaginalis infection among male partners of women with trichomoniasis and factors associated with infection by recruiting patients from 3 public clinics in the United States. Male partners were tested for concordant T. vaginalis infection, defined as a positive urethral culture, urine culture, or urine polymerase chain reaction (PCR) result. A subset of men also provided a semen sample for T. vaginalis culture and PCR. Factors associated with concordant infection were determined from bivariable and multivariable analyses.Results. We enrolled 540 women with trichomoniasis (diagnosed using wet mount microscopy and/or culture) and 261 (48.4%) of their male partners. T. vaginalis infection was detected in 177 (71.7%) of 256 male partners (95% confidence interval [CI], 66.0%– 77.3%), of whom 136 (77.3%) were asymptomatic. A vaginal pH of >4.5 in a woman was independently associated with infection in the male partner (adjusted odds ratio, 2.5; 95% CI, 1.0– 6.3). Younger male age (20– 29 and 30– 39 years) was also found to be an independent risk factor for concordant trichomoniasis.Conclusions. The majority of male partners of women with trichomoniasis were infected; however, few factors predicted infection. T. vaginalis causes a highly prevalent STI, necessitating vastly improved partner management, application of sensitive nucleic-acid based testing, and better clinical recognition.

Etiology of Genital Ulcers and Prevalence of Human Immunodeficiency Virus Coinfection in 10 US Cities

To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city. Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV. H. ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%). T. pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%). HSV was detected in >/=50% of specimens from all cities except Memphis (42%). HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%). These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities.

High Rates of Trichomonas vaginalis among Men Attending a Sexually Transmitted Diseases Clinic: Implications for Screening and Urethritis Management

Trichomonas is a cause of nongonococcal urethritis (NGU); however, studies of its prevalence in men have been hampered by the lack of sensitive diagnostics. DNA amplification allows for reappraisal of the extent of infection in men. Men attending a sexually transmitted diseases clinic were tested for trichomonas, chlamydia, and gonorrhea. The prevalence of these pathogens was 17%, 19.6%, and 17.7% respectively. In men with NGU, 19.9% were infected with trichomonas. These data have implications for treatment of NGU and control of trichomoniasis.

Local and Systemic Cytokine Levels in Relation to Changes in Vaginal Flora

BACKGROUND Bacterial vaginosis (BV) is associated with increased risk of obstetrical and gynecologic complications and acquisition of sexually transmitted diseases. Despite this, very little is known about the pathogenesis of this disease. METHODS Interleukin (IL)-1 beta , tumor necrosis factor- alpha , IL-6, and IL-8 concentrations in vaginal wash and serum samples from women with normal flora, intermediate flora, and BV (determined by Nugent criteria) were measured by enzyme-linked immunosorbent assay. RESULTS Cytokine levels were not different between women with intermediate flora and women with BV. Women with either intermediate flora or BV had significantly higher concentrations of IL-1 beta in vaginal wash samples than did women with normal flora. The presence of IL-1 beta in vaginal wash samples was associated with >30 Gardnerella or Prevotella morphotypes per high-power field, as detected by Gram staining of vaginal swab specimens. Variation in the numbers of Lactobacillus and Mobiluncus species did not influence local cytokine levels. Serum cytokine levels were not influenced by any changes in vaginal flora. CONCLUSIONS Women with intermediate flora generate significant cytokine responses. It is possible that the risks associated with BV may also affect women with intermediate flora and that appropriate treatment may reduce such risk.

Prevalence of Trichomonas vaginalis Isolates with Resistance to Metronidazole and Tinidazole

ABSTRACT Clinical isolates of Trichomonas vaginalis were obtained from women consecutively enrolled in a study of partner notification. Testing of susceptibility to metronidazole and tinidazole was performed. Resistance to metronidazole and tinidazole was present in 17/178 (9.6%) and 1/178 (0.56%) strains, respectively. In vitro resistance was poorly correlated with clinical response to treatment.