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[STDs] Atlas of Vaginal Infections

Atlas of Vaginal Infections. Vulvovaginal Candidiasis, Bacterial Vaginosis, Trichomoniasis and Other Vulvovaginal Syndromes

OVERVIEW


Vulvovaginal yeast infections, bacterial vaginosis, and trichomoniasis are among the most common reasons for which women seek health care in the United States and probably in other industrialized countries. All sexually active women with trichomoniasis or new onset of bacterial vaginosis, and many with candidiasis, should be evaluated for other common STDs.

Vulvovaginal Candidiasis 

Vulvovaginal candidiasis (VVC) generally is not sexually transmitted and most symptomatic episodes do not result from exogenous infection. Rather, Candida albicans and sometimes C. glabrata are normal commensal flora of the vagina and colon, and clinically evident VVC results when known factors (e.g., suppression of vaginal bacterial flora by antibiotics, hyperglycemia in diabetes) and unknown ones result in proliferation of yeasts or development of an allergic response to them. A small minority of infections may be acquired from sex partners with genital or oral colonization with Candida. Symptomatic VVC typically is accompanied by external genital symptoms and signs (vulvitis), yet vaginal fluid leukocytosis usually is absent.

Uncomplicated VVC is defined as sporadic, infrequent cases of mild or moderate severity in immunocompetent women who are likely to be infected with C. albicans. Complicated VVC includes
recurrent infections, clinically severe cases, infection with C. glabrata, and VVC in immunocompromised women or those with uncontrolled diabetes, and requires more intensive or more prolonged treatment and may warrant ongoing prophylactic therapy. Single-dose oral treatment with fluconazole is effective against uncomplicated VVC and often is preferred by patients over intravaginal therapy. Effective vaginal preparations for treatment of VVC are available over the counter. However, self-treatment for vaginal discharge risks delayed diagnosis of STDs, and should be restricted to patients with previous professionally diagnosed VVC who have typical recurrent symptoms. 

Bacterial Vaginosis

Bacterial vaginosis (BV) is characterized by overgrowth of commensal vaginal bacteria, including Gardnerella vaginalis, Mobiluncus species, Prevotella species, Mycoplasma hominis, and numerous anaerobes. Hydrogen peroxide-producing Lactobacillus crispatus and other lactobacilli, which maintain an aerobic, acidic milieu in the healthy vagina, are absent in BV or present in greatly reduced amounts. One hypothesis of pathogenesis is that failure of Lactobacillus colonization is the initiating event in BV, but the specific causes are unknown. Novel bacterial vaginosis-associated bacteria types 1, 2, and 3 (BVAB-1, -2, and -3) have been identified by 16s ribosomal analysis but not yet cultured. They appear to be specifically associated with the syndrome, but it remains uncertain whether BVAB have a direct etiologic role in BV. There is little or no inflammatory response in BV and leukocytes usually are not found in vaginal fluid, hence the term vaginosis, not vaginitis.

Bacterial vaginosis is associated with sexual intercourse and with the same epidemiologic markers as
classical STDs, such as multiple sex partners, new partners, and past history of STDs, but whether BV should be classified as an STD is controversial. Direct sexual transmission clearly occurs in women who have sex with women, through shared vaginal secretions, and almost all female sex partners of women with BV have the syndrome themselves. It has been reported that BV can occur in sexually inexperienced women, i.e., without history of penile-vaginal intercourse. However, recent studies show the syndrome to occur rarely if ever in women who have had no vaginal sexual exposures, including cunnilingus, suggesting that the initial occurrence of BV may require exogenous infection with a sexually transmitted pathogen. On the other hand, no recognized sexually transmitted organism has been directly linked with BV, and treatment of women’s male partners does not apparently influence the rate of recurrence following treatment, although it is uncertain whether optimal therapies have been employed. Whether or not BV is an STD in the usual sense, affected women are at elevated risk for other STDs, and routine screening and STD prevention counseling are indicated for women with the syndrome.

Bacterial vaginosis is associated with elevated risks of pelvic inflammatory disease (PID), premature
labor, and other complications of labor and delivery, but in a large randomized controlled trial the frequency of adverse pregnancy outcomes was not reduced by treatment of BV in pregnant women. Many women with BV attempt self-treatment with vaginal douching, but vaginal douching itself predisposes to BV and is epidemiologically linked with PID and ectopic pregnancy. Clinicians should discourage women from douching for any reason, including vulvovaginal “hygiene,” odor, discharge, or following menstruation or intercourse. Treatment of BV is based primarily on anti-anaerobic antibiotics, ideally with drugs like metronidazole that do not inhibit Lactobacillus, which might retard repopulation of the vagina with protective biota. 

Trichomoniasis

Trichomoniasis is a common sexually transmitted infection caused by the unicellular parasite Trichomonas vaginalis. Apparent exceptions to sexual transmission generally are explained by delayed diagnosis of longstanding infection, or by acquisition from chronically infected sex partners. Symptomatic trichomoniasis is associated with an inflammatory response and vaginal leukocytosis and is accompanied by anaerobic bacterial overgrowth and depletion of lactobacilli, as in BV. Other STDs, such as gonorrhea or chlamydial infection, often are present. Infected men usually are asymptomatic, but some have nongonococcal urethritis (NGU), and T. vaginalis can be identified by nucleic acid amplification test (NAAT) in about 5% of NGU cases. Heretofore widely considered a trivial infection, trichomoniasis is emerging  as an important STD that causes significant morbidity in women both directly and through enhanced susceptibility to sexually transmitted HIV. Evidence is mounting that routine screening and other public health prevention measures are warranted, a case made stronger by development and increasing availability of T. vaginalis NAATs.

Single-dose treatment with oral metronidazole is the usual therapy, but is only about 90% effective; multiple-dose regimens are more reliable. Tinidazole, a related drug, is more expensive than metronidazole but perhaps more effective, especially in single doses and in men. Intravaginal metronidazole is ineffective. Occasional strains of T. vaginalis are resistant to both drugs, making treatment difficult. High-dose intravenous metronidazole sometimes is effective, and case reports suggest that intravaginal therapy with paromomycin or furazolidone may be useful options.

Other Vulvovaginal Syndromes

Uncommon causes of vulvovaginal infection or increased vaginal discharge include retained foreign bodies (e.g., tampons), enterovaginal fistulas, and estrogen deficiency. Physiologic leucorrhea, i.e., fluctuations in the quantity or character of cervicovaginal secretions, explains some women’s complaints of increased vaginal discharge. Idiopathic vulvodynia and desquamative inflammatory vaginitis are vexing clinical problems that are not attributable to any known STD. 

EPIDEMIOLOGY

Incidence and Prevalence

• Among women attending STD or reproductive health clinics, VVC is diagnosed in 20–25%, BV in
10–20%, trichomoniasis in 5–15%
• Most women age 15–40 years experience one or more episodes of VVC
• In a population-based U.S. sample (NHANES) 2001–2004, 3.2% of women had trichomoniasis and
33% had BV

Transmission

• Vaginal colonization with Candida species is present in 10–20% of healthy women of reproductive
age, often originating from colonic reservoir
• Transmission of BV uncertain
° Associated with sexual activity, but sexual transmission between males and females remains uncertain
° Directly transmitted between female sex partners through shared vaginal secretions
• T. vaginalis is sexually transmitted and acquired

Age

• No particular predilection
• All three syndromes are most frequent in young women

Sex

• BV has no known male counterpart
• Male partners of women with VVC sometimes have penile Candida dermatitis or balanitis 
• T. vaginalis colonizes male urethra and periurethral glands
° Usually asymptomatic
° Accounts for ~5% of NGU

Sexual Orientation

• BV is common in WSW; female sex partners of women with BV almost invariably have BV themselves
• WSW are not apparently at either increased or reduced risk for VVC or trichomoniasis, but few data
available

Other Risk Factors

• Douching increases risk of BV, probably by disrupting normal vaginal ecology
• Diaphragm, contraceptive sponge, and nonoxynol-9–based spermicides apparently predispose to BV and perhaps VVC
• Antibiotic therapy predisposes to VVC and perhaps BV
• Poorly controlled diabetes mellitus predisposes to vaginal colonization with Candida and VVC, sometimes severe
• Except for overt AIDS, HIV infection is not associated with substantially enhanced risk of VVC, despite earlier reports to the contrary; however, HIV infection may impair response of VVC to treatment
• Tight-fitting garments probably do not predispose to VVC, notwithstanding common beliefs.

HISTORY

Incubation Period

• VVC usually is not attributable to exogenous infection with Candida species; occurs in previously colonized women as result of enhanced growth of Candida or allergic reaction to it
• Symptoms of trichomoniasis or BV often begin a few days to 4 weeks after sexual exposure to new
or infected partners

Symptoms

Vulvovaginal Candidiasis

• Vulvar burning pain or pruritus
• “External” dysuria from contact of urine with inflamed introitus and labia
• Vaginal discharge usually absent or scant
• Usually no malodor (contrary to popular belief)

Bacterial Vaginosis

• Genital malodor, often described as “fishy,” is the most common symptom
• Odor may be more prominent following intercourse; alkalinity of semen volatilizes amine products
of anaerobic bacterial metabolism 
• Increased vaginal discharge
° Inflammatory response and leukocytes are usually absent; therefore discharge does not cause
prominent staining of underclothes
• Often asymptomatic

Trichomoniasis

• Increased vaginal discharge, often profuse
° Staining of underclothes (secretions are inflammatory with elevated leukocytes)
• Malodor, often “fishy”; sometimes prominent after vaginal intercourse (See Bacterial Vaginosis)
• Vulvar pruritus
• Most prevalent cases are asymptomatic

Epidemiologic History

• Risk factors for STD often are present in women with BV or trichomoniasis
• STD risk is not associated with VVC
• Antibiotic use precedes some VVC and BV
• Women with BV or VVC often give history of prior episodes 

PHYSICAL EXAMINATION

Vulvovaginal Candidiasis

• Vulvar erythema, sometimes with edema or superficial fissures
• Typical discharge is scant, clumped, white, adherent to vaginal mucosa, but appearance is quite
variable and can include flocculent or purulent-appearing exudate
• Complicated or severe VVC: Vulvar erythema or edema, often with superficial fissures and
excoriation

Bacterial Vaginosis

• Discharge typically white, homogeneous, smoothly coating vaginal walls or labia; scant to moderate
in amount
• Usually no erythema or other inflammatory signs
• Signs of MPC may be present

Trichomoniasis

• Discharge typically copious and purulent (creamy, yellow, or brown)
• Bubbles in vaginal fluid are said to be highly specific for trichomoniasis, but usually absent
• Mucosal erythema may be present
• Cervix may show signs of MPC
• Occasional petechiae on ectocervix (“colpitis macularis,” “strawberry cervix”)


DIAGNOSTIC APPROACH

The first step in evaluating a woman with increased vaginal discharge or other vulvovaginal complaints is a speculum examination to determine whether abnormal secretions originate from the vagina or cervix. The character of the vaginal discharge is assessed and the vaginal mucosa and vulva are inspected for erythema, edema, ulcers, and other lesions. Table 19-1 displays the usual characteristics of VVC, trichomoniasis, BV, and uninfected women. An accurate office diagnosis usually can be made by determination of the pH of vaginal secretions, testing for amine (fishy) odor on addition of 10% KOH, and microscopy of vaginal fluid by saline and KOH wet mounts, Gram stain, or all three. However, saline microscopy is only 60–70% sensitive for T. vaginalis in symptomatic trichomoniasis and probably is <50% sensitive in asymptomatically infected women. Culture for T. vaginalis improves sensitivity, but NAAT is now the test of choice and is increasingly available in clinical laboratories. Culture for yeasts also may be helpful when VVC is suspected but not confirmed microscopically, but positive cultures for Candida species must be interpreted with caution because many women are colonized without symptoms. Rapid, office-based chemical tests for BV flora or chemical markers may also be useful; a rapid test for sialidase, a product of anaerobic metabolism, is in wide use. Screening tests for chlamydial infection, gonorrhea, syphilis, and HIV infection should be routine in all women with trichomoniasis or initial episodes of BV, and in selected women with VVC or recurrent BV, depending on sexual history 

LABORATORY DIAGNOSIS

Vulvovaginal Candidiasis

• Vaginal fluid pH ≤4.5
• Negative amine odor with 10% KOH
• Vaginal fluid microscopy (Gram-stained smear or saline mount) demonstrates pseudohyphae or yeasts in ~80% of patients; visualization of fungal elements may be aided by KOH wet mount, which
digests cells and highlights yeasts and pseudohyphae
• PMNs usually absent or scant
• Visualization of yeasts alone (without pseudohyphae) is not diagnostic; may indicate asymptomatic
colonization
• Isolation of Candida species may be helpful if microscopy is negative, but may be positive due to
asymptomatic colonization

Bacterial Vaginosis

• Vaginal fluid pH > 4.5 (usually ≥4.7)
• Amine odor with 10% KOH (liberates volatile amines produced by anaerobic bacteria)
• Saline mount or Gram-stained smear showing clue cells, i.e., epithelial cells with granular appearance and indistinct borders due to adherent bacteria
• PMNs usually absent
• Gram stain shows profusion of mixed gram-positive and gram-negative bacteria, and absence of
Gram-positive bacilli typical of Lactobacillus species
• Test for sialidase, liberated by vaginal bacteria in BV, (e.g., BVblue) may be a useful diagnostic aid 


Trichomoniasis

• Vaginal fluid pH >4.5 (usually ≥5.0)
• Motile trichomonads (60–70% sensitive) and predominant PMNs on saline microscopy of vaginal
secretions
• NAAT or culture for T. vaginalis if trichomoniasis suspected and microscopy negative
• Clue cells and positive amine odor test usually present, as in BV.

TREATMENT

Vulvovaginal Candidiasis

Uncomplicated VVC

• Fluconazole 150 mg PO (single dose)
• Intravaginal imidazole
° Several creams or suppositories are available (butoconazole, clotrimazole, miconazole, terconazole, or tioconazole)
° Administer once daily for 3–7 days (single-dose regimens not recommended)
° Several are available over the counter
• Nystatin vaginal tablets 100,000 units once daily for 14 days

Complicated VVC

• Severe VVC or immunocompromised patient
° Fluconazole 150 mg PO twice, 3 days apart; or
° Vaginal imidazole for 7-14 days
° Correct modifiable conditions (e.g., diabetes control)
• VVC caused by C. glabrata or other non-albicans species
° Imidazole therapy other than fluconazole, e.g., a vaginal imidazole for 7-14 days
° Boric acid in gelatin capsules, 600 mg vaginally once daily for 14 days
• Prevention of recurrent VVC
° Fluconazole 150-200 mg PO once weekly; or
° Vaginal imidazole or nystatin once weekly

Partner Management

• Routine referral of partners is not recommended
• Male partners with symptoms that suggest penile dermatitis may benefit from topical antifungal therapy 

Bacterial Vaginosis

Vaginal douching should not be used and should be assertively discouraged for treatment or prevention of BV or for vaginal hygiene. Currently available Lactobacillus preparations and dairy products (e.g.,  yogurt) do not contain physiologic Lactobacillus strains that produce hydrogen peroxide, do not successfully colonize the vagina, and are ineffective for treatment or prophylaxis, whether used orally or intravaginally. Research is under way to develop therapeutic products based on L. crispatus or other human lactobacilli.

Treatments of Choice

• Metronidazole 500 mg PO bid for 7 days
• Metronidazole gel 0.75% 5 g intravaginally once daily for 5 days
• Clindamycin 2% cream 5 g intravaginally once daily at bedtime for 7 days

Alternatives

• Tinidazole 2.0 g PO once daily for 3 days
• Tinidazole 1.0 g PO once daily for 5 days
• Clindamycin 300 mg PO bid for 7 days
• Clindamycin vaginal ovules 100 mg intravaginally once daily at bedtime for 3 days

Follow-up

• Reevaluate after 1-2 weeks if symptoms persist

Partner Management

• Evaluate male partners of women with first-episode BV
• No treatment is recommended for male partners without evidence of STD
• Advise WSW that their female partners are likely to have BV

Trichomoniasis

Treatments of Choice

• Tinidazole 2.0 g PO, single dose
• Metronidazole 2.0 g PO, single dose

Alternative Treatments

Multiple-dose therapy is indicated whenever trichomoniasis persists or recurs after treatment of patient and sex partners.
• Tinidazole 500 mg PO bid for 5 days
• Metronidazole 500 mg PO bid for 7 days

Follow-up

• Both reinfection and treatment failure (with single-dose therapy) are common
• Reevaluate 1 week after treatment if symptoms persist
• Rescreen women for T. vaginalis 3 months after treatment, using NAAT or culture

Partner Management

• Evaluate partners for urethritis and other STD
• Treat routinely with tinidazole 2.0 g (single dose) or metronidazole 2.0 g PO (single dose)
• EPT has uncertain efficacy but is warranted if partner is unlikely to attend for care

PREVENTION

Vulvovaginal Candidiasis

• Manage predisposing causes (e.g., diabetes control)
• Avoid unnecessary antibiotic therapy
• Prophylactic antifungal therapy in patients with recurrent VVC

Bacterial Vaginosis

• Recurrent BV is common, vexing, and difficult to prevent
• Condoms may help prevent some episodes in women with recurrent BV
• Treatment of female partners may help prevent reinfection
• Avoid douching

Trichomoniasis

• Treatment of sex partners
• Routine STD prevention measures (partner selection, condoms, etc.).

Candida vulvovaginitis
19–1. Candida vulvovaginitis; erythema and edema of labia minora 
and scant, clumped white exudate  

CASE 1

Patient Profile Age 20, university student, sexually active with one male partner

History Vulvar itching and slightly increased vaginal discharge for 2 days
Examination Faint erythema of vaginal introitus and labia minor; plaques of clumped white discharge on vaginal mucosa and labia

Differential Diagnosis VVC; consider trichomoniasis, BV, MPC

Laboratory Vaginal fluid pH 4.0; amine odor test negative; microscopy of vaginal fluid mixed with KOH solution showed yeasts and pseudohyphae; saline microscopy negative for motile trichomonads; cervical NAATs for C. trachomatis and N. gonorrhoeae (negative)

Diagnosis VVC

Treatment Fluconazole 150 mg PO (single dose)

Sex Partner Management Patient advised that partner need not be examined unless symptomatic
(e.g., penile irritation or rash)

Comment Screening test for C. trachomatis was obtained on the basis of age ≤20 years; tests for other STDs optional.

Microscopic findings in vulvovaginal candidiasis
19–2. Microscopic findings in vulvovaginal candidiasis. a. 10% KOH digest of vaginal secretions showing pseudohyphae of C. albicans. b. Gram-stained smear of vaginal secretions, showing typically mottled, gram-positive pseudohypha of C. albicans and multiple Lactobacillus morphotypes. . Gram stain and KOH microscopy are similarly effective in diagnosis of VVC.

Bacterial vaginosis
19–3. Bacterial vaginosis; white, homogeneous discharge smoothly coating the vaginal mucosa.  

CASE 2

Patient Profile Age 22, single, photographer’s assistant

History Increased vaginal discharge with unpleasant odor for 1 week; “strong” odor after unprotected
vaginal sex; monogamous 1 month with a male partner; history of chlamydia and genital warts 2 years earlier

Examination External genitals normal; homogeneous white vaginal secretions at introitus and smoothly coating vaginal mucosa; cervix showed small area of ectopy, with slightly cloudy mucus in os; bimanual examination normal

Differential Diagnosis Probable BV; consider trichomoniasis, VVC, chlamydia, gonorrhea, physiologic discharge

Laboratory Vaginal fluid pH 5.0; amine (fishy) odor with addition of 10% KOH; saline wet-mount microscopy showed clue cells, no trichomonads, rare PMNs; cervical NAATs for C. trachomatis and N. gonorrhoeae, RPR, HIV serology (all negative)

Diagnosis Bacterial vaginosis

Treatment Metronidazole 500 mg PO bid for 7 days

Partner Management Advised to refer her partner for STD evaluation to exclude other STDs; his examination was normal, not treated 

19–4. Microscopic findings in bacterial vaginosis. 
a. Clue cell (arrow) adjacent to normal vaginal epithelial cells. The clue cell has an indistinct, ragged margin and a refractile, granular appearance due to large numbers of adherent bacteria. 
b. Gram-stained smear of secretions in bacterial vaginosis, showing myriads of small, pleomorphic, gram-negative and gram-positive bacteria that heavily coat a clue cell; Lactobacillus morphotypes are not seen. 
c. Gram-stained smear of normal vaginal fluid, showing epithelial cells and predominant flora of large, gram-positive bacilli (Lactobacillus species).  

Purulent vaginal discharge in trichomonal vaginitis.
19–5. Purulent vaginal discharge in trichomonal vaginitis. Bubbles due to gas production are seen in
a minority of cases but are highly specific for trichomoniasis. Mucopurulent cervical discharge and a
small area of edematous cervical ectopy also are present.
 
 

CASE 3

Patient Profile Age 24, single, unemployed, recovering heroin addict, referred from a drug rehabilitation agency

History Increased vaginal discharge and slight vulvar pruritus for 2 weeks; one male partner for 6 months

Examination External genitals normal; copious, malodorous, faintly yellow vaginal discharge with bubbles; small area of cervical ectopy and mucopurulent cervical discharge; no adnexal tenderness or
masses
Differential Diagnosis Trichomoniasis, bacterial vaginosis; probable MPC; rule out vulvovaginal candidiasis, gonorrhea, chlamydial infection

Laboratory Vaginal fluid pH 5.5; amine odor test positive; saline preparation showed PMNs, motile
trichomonads, few clue cells; Gram-stained endocervical smear showed many PMNs without GND; cultures for C. trachomatis (negative) and N. gonorrhoeae (positive); VDRL (negative); HIV serology (positive)

Diagnosis Trichomonal vaginitis; gonorrhea with MPC; HIV infection

Treatment Metronidazole 2.0 g PO (single dose); patient was contacted after N. gonorrhoeae culture
result was reported positive and given cefixime 400 mg PO and azithromycin 1.0 g PO (both single dose) 

Partner Management Partner contacted; treated with metronidazole, cefixime, and azithromycin; also found to have gonorrhea, HIV-positive

Comment Trichomoniasis often is associated with other STDs, such as gonorrhea. The clinically evident MPC could be the result of gonorrhea, trichomoniasis, or both. The patient and her partner were referred to an infectious diseases clinic for HIV/AIDS clinical care. 


Saline wet mount microscopy of vaginal secretions in trichomoniasis
19–6. Saline wet mount microscopy of vaginal secretions in trichomoniasis, showing
T. vaginalis (arrows) and leukocytes. In actual use, trichomonads are readily distinguished from leukocytes by their motility.
  

Frothy vaginal discharge in trichomonal vaginitis
19–7. Frothy vaginal discharge in trichomonal vaginitis.  

Cervical petechiae (“colpitis macularis,” “strawberry cervix”)
19–8. Cervical petechiae (“colpitis macularis,” “strawberry cervix”), an uncommon
but specific manifestation of trichomoniasis
  

Clumped vaginal exudate and mucosal erythema in vulvovaginal candidiasis
19–9. Clumped vaginal exudate and mucosal erythema in vulvovaginal candidiasis.  

Balanitis due to C. albicans in the uncircumcised partner of a woman with VVC
19–10. Balanitis due to C. albicans in the uncircumcised partner of a woman with VVC, showing
punctate erythema of glans penis.
  

REFERENCES
H. Hunter Handsfield, MD, Color Atlas & Synopsis of Sexually Transmitted Diseases, Third Edition.

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Free Medical Atlas: [STDs] Atlas of Vaginal Infections
[STDs] Atlas of Vaginal Infections
Atlas of Vaginal Infections. Vulvovaginal Candidiasis, Bacterial Vaginosis, Trichomoniasis and Other Vulvovaginal Syndromes
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