Vaginitis

1. What every clinician should know

Vaginitis is a condition that encompasses a spectrum of vulvovaginal symptoms. This chapter will focus on two of the most common causes of vaginitis. Yeast vaginitis (vulvovaginal candidiasis) is discussed in another chapter.

Bacterial vaginosis (BV) is the most common type of vaginitis. It is characterized by a shift in normal vaginal flora to a predominantly anaerobic environment. As a result, the number of Lactobacilli organisms, which produce peroxide and lower the pH of the vagina, is reduced. This shift in vaginal micorflora can lead to symptomatic vaginitis, but not all women with clinical BV have symptoms. When symptomatic, women may present to with vaginal discharge, odor, and/or vulvo-vaginal irritation. The color of this discharge can vary from clear to white to gray. Women may describe an offensive odor which may be characterized as “fishy.”

Trichomonas vaginalis (TV) is common type of vaginitis and the second most common sexually transmitted infection in the world and the United States. TV is an anaerobic flagellated protozoan parasite that inhabits the male and female genital tracts and is transmitted through coitus. Most men and a significant percentage of women are asymptomatic of TV infection. When symptoms occur, female patients often report malodorous discharge which can be associated with vulvo-vaginal irritation and vaginal spotting. These symptoms are very difficult to distinguish from BV. Patients with TV may also report dyspareunia or abdominal/pelvic pain, dysuria, and pruritus. Unique to TV, it is more prevalent in older women.


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BV and TV share common risk factors and associations. These infection are more common in certain populations of women and include those who are:

  • sexually active, especially with a new partner or multiple partners
  • have a concurrent or history of a sexually transmitted infection
  • do not use condoms
  • engage in douching

2. Diagnosis and differential diagnosis

Diagnosis: Bacterial vaginosis

Methods available for the diagnosis of BV include microscopy, gram stain, and point of care tests. A Nugent Score, is the gold standard, but is mostly used for research purposes. A Nugent score is determined by reviewing a gram stain of the vaginal fluid for characteristic microorganisms and requires training to interpret. If the Nugent score is greater than or equal to 7, the patient has BV.

BV is most often diagnosed using clinical criteria (Amsel’s criteria). 3 of 4 criteria are required to make the diagnosis:

  • vaginal discharge
  • elevated vaginal pH (> 4.5) obtained from the vaginal side wall
  • a positive whiff test (an amine odor produced by the addition of potassium hydroxide (10% KOH) to the vaginal fluid)
  • at least 20% of the epithelial cells present are clue cells (epithelial cells covered with bacteria) on microscopy.

Point of care tests are available for physicians who do not have microscopy or laboratory support available. These include the DNA probe-based test for high concentrations of G. Vaginalis which is the AFIRM VP III® and the test card for Prolineaminopeptidase activity which is the PIP Activity TestCard®

Diagnosis: Trichomonas vaginalis

The current gold standard for diagnosis of TV is culture in Diamond’s media. The TVinPouch® is commercially available. Cultures are incubated at 37° C and inspected up to five days for the presence of motile trichomonads. The sensitivity of culture is 87-90% and specificity is reported as 92-100%.

Microscopy is more commonly used that culture, because it does not require laboratory support or incubation. Vaginal fluid is combined with normal saline and inspected for the presence of motile trichomonads. Microscopy is less sensitive than culture (60%) but 100% specific.

Nucleic acid amplification (NAAT) and polymerase chain reaction (PCR) for TV are available in some large centers but have been used mostly for research purposes. PCR has improved sensitivity and specificity over culture and microscopy, 90% and 97-100% respectively. This method may replace the more commonly used diagnostic techniques in the future when PCR is more readily available.

Point of care tests are also available for the diagnosis of TV. These include the OSOM® rapid test, which detects TV antigen, and the AFFIRM® test, which is a nucleic acid amplification probe for TV, BV, and yeast.

Differential diagnoses
Yeast

Vaginal candidiasis or vaginal yeast infections are a common cause of vaginal discharge and irritation. Yeast infections are often associated with vulvo-vaginal itching. On microscopy, the diagnosis is made by the visualization of psuedohyphae or budding yeast. Adding KOH to the vaginal fluid may enhance the examiner’s ability to see yeast on a microscopy specimen.

Cervicitis

Cervicitis is general description of cervical inflammation which may be associated with sexually transmitted infections such as gonorrhea and Chlamydia. Patients may present with vaginal discharge, but this condition is often asymptomatic. The examiner may see leukocytes (neutrophils or white blood cells) on microscopy (leukorrhea).

Desquamative inflammatory vaginitis

Inflammatory vaginitis is an uncommon cause of vaginal discharge and irritation. It is not associated with a specific pathogen or known to be infectious. It is most often a diagnosis of exclusion, especially in women who continue to have vaginal discharge despite therapy for common causes of vaginitis. On microscopy, the examiner will identify leukocytes. It is important to exclude other more common and infectious causes of vaginal leukorrhea, including Trichomonas, BV, yeast, and pelvic inflammatory disease (PID).

Atrophic vaginitis

Atrophic vaginitis is characterized by irritation secondary to decreased vaginal secretions. This condition results from decreased circulating estrogen and is most often encountered in postmenopausal women. On microscopy, the examiner may note parabasal cells. Atrophic vaginitis usually responds to topical estrogen therapy.

3. Management

Bacterial vaginosis

Bacterial vaginosis is most often treated with antimicrobial therapy.

Oral
  • Metronidazole 500mg orally twice daily x 7 days
  • Tindazole 2gm by mouth daily x 2 days
  • Tindazole 1gm by mouth daily x 5 days
  • Clindamycin 300mg orally twice daily x 7 days
Topical
  • Metronidazole 0.75% gel per vagina daily x 5 days
  • Clindamycin 2% gel per vaginal daily x 7 days
Trichomonas vaginalis

Trichomonas vaginalis should be treated with oral antimicrobial therapy, topical therapy is not recommended.

  • Metronidazole 2000mg po orally once
  • Tindazole 2000mg po orally once
  • Metronidazole 500mg orally twice daily x 7 days (preferred therapy in HIV positive women due to high failure rates with single dose therapy)

4. Complications

Sequelae of infection

BV and TV can both be associated with an increased risk of acquiring sexually transmitted infections, pelvic inflammatory disease (PID), human immunodeficiency virus (HIV), and developing post-gynecologic surgical infections. Treatment of BV prior to benign gynecologic surgery decreases the risk of post-operative infection.

During pregnancy, symptomatic BV and TV have been associated with preterm birth, premature rupture of membranes, chorioamninitis, and postpartum infection. However, current evidence does not support treatment of BV and TV during pregnancy in order to prevent adverse pregnancy outcomes.

Allergic reaction

Some patients are allergic to metronidazole. In the case of BV, there are alternative anti-microbial therapies. However, in the case of patients with TV who have an immediate hypersensitivity reaction (hives or anaphylaxis) to metronidazole, there are limited options for therapy. Alternative therapies for TV have proven very ineffective. Because tindazole is in the same antimicrobial class as metronidazole, it is not recommended in the case of an immediate hypersensitivity reaction. Patients can be desensitized to metronidazole either through progressive incremental intravenous or oral administration.

5. Prognosis and outcome

Recurrence
BV

BV recurs in approximately one third to half of women. Some women are more prone to recurrent BV. Patients that have more than 3-6 episodes of BV per year may require prolonged therapy in order to decrease recurrence.

TV

Approximately 5% of cases of TV are not successfully treated by the recommended single dose of metronidazole. Repeat or prolonged therapy with metronidazole or treating with Tindazole may improve success. In some instances, the organism has become resistant to metronidazole and may require prolonged therapy and consultation with an infectious diseases specialist.

6. What is the evidence for specific management and treatment recommendations

Workowski, KA, Berman, S. “Sexually transmitted diseases treatment guidelines, 2010”. MMWR Recomm Rep Dec. vol. 59. 17. pp. 1-110. (The CDC STD Guidelines are an excellent source for clinicians treating vaginitis. These guidelines are compiled by a panel of vaginitis experts and are based on the best available literature.)

Nugent, RP, Krohn, MA, Hillier, SL. “Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation”. J Clin Microbiol. 1991. pp. 297-301. (This article determined the most reliable and reproducible means for vaginal fluid gram stain interpretation for BV.)

Amsel, R, Totten, PA, Spiegel, CA. “Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations”. Am J Med. vol. 74. 1983. pp. 14-22. (The findings of this article provided evidence for the use of clinical (Amsel’s) criteria to diagnosis BV.)

Sobel, JD, Ferris, D, Schwebke, J. “Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis”. Am J Obstet Gynecol. vol. 194. 2006. pp. 1283-9. (This multicenter randomized trial demonstrated that women on suppressive therapy for recurrent bacterial vaginosis had fewer recurrences following suppression than placebo. These findings support the use of twice weekly metronidazole gel in women with recurrent BV.)

Hillier, SL, Nugent, RP, Eschenbach, DA. “Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant”. N Engl J Med. vol. 333. 1995. pp. 1737-42. (This multi-clinical trial enrolled with women with no known risk factors for preterm birth, and determined the prevalence of BV in this population. The primary outcome for this study was preterm delivery (<37 weeks gestation). The presence of BV was associated with increased risk of preterm delivery of a low birth weight infant.)

Sutton, M, Sternberg, M, Koumans, EH. “The prevalence of infection among reproductive-age women in the United States, 2001–2004”. Clin Infect Dis. vol. 45. 2007. pp. 1319-26. (These data are from the NHANES trial. Prior to this study, estimating the prevalence of Trichomonas in American women has been limited by the fact that this is not a reportable disease. These data also raise awareness of the racial discrepancy in TV infections.)

Schwebke, JR, Burgess, D. “Trichomoniasis”. Clin Microbiol Rev. 2004. pp. 794-803. (Dr. Schwebke is a recognized expert in Trichomonas vaginalis infections. This is an excellent review of the organism, epidemiology, diagnosis, and management.)

Krieger, JN, Tam, MR, Stevens, CE. “Diagnosis of trichomoniasis. Comparison of conventional wet-mount examination with cytologic studies, cultures, and monoclonal antibody staining of direct specimens”. JAMA. vol. 259. 1988. pp. 1223-7. (This article demonstrates the improved sensitivity of culture over microscopy for the diagnosis of Trichomonas.)

Helms, DJ, Mosure, DJ, Secor, WE. “Management of in women with suspected metronidazole hypersensitivity”. Am J Obstet Gynecol. vol. 198. 2008. pp. 370-7. (Given the limited effective treatments for Trichomonas, this article is an excellent resource. It provides a metronidazole desensitization protocol, which can be used to treat patients with metronidazole hypersensitivity.)