1. DIAGNOSIS AND TREATMENT OF VAGINITIS
Stephanie N. Taylor, MD
LSUHSC Department of Medicine
Section of Infectious Diseases

2. DISCLOSURE
I have no financial interests or other relationship with manufacturers of commercial products, suppliers of commercial services, or commercial supporters. My presentation will not include any discussion of the unlabeled use of a product or a product under investigational use.

3. VAGINITIS
Inflammation of the vagina leading to vaginal irritation and discharge
Both cervicitis and vaginitis can cause vaginal discharge and distinction can be difficult (Speculum Exam)

4. ETIOLOGY OF VAGINITIS YEAST (CANDIDA SP.) TRICHOMONAS VAGINALIS
BACTERIAL VAGINOSIS
ALLERGIC RXN, ESTROGEN DEF., etc.

5. VULVOVAGINAL CANDIDIASIS
Candida albicans, Candida glabrata, etc. colonize vagina
Proliferation or allergic reaction caused by known and unknown factors (Antibiotic use, diabetes, pregnancy, etc.)
Estimated that >75% of women will have at least one episode during lifetime

6. VULVOVAGINAL CANDIDIASIS
VVC causes 20-25% of vaginitis in STD clinics
Not truly sexually transmitted - males can acquire the organism however (Candida balanitis or dermatitis)

7. VULVOVAGINAL CANDIDIASIS
Symptoms
Vulvar pruritis, burning or pain
“External dysuria” - 20 to inflammed labia
Complaint of discharge
Physical Examination
Vulvar erythema, edema, fissures, vulvar dermatitis with satellite lesions
Clumped, white, adherent discharge - classic
Occasionally scant, homogeneous, purulent

8. VULVOVAGINAL CANDIDIASIS
Diagnosis
KOH Prep - Pseudohyphae in ~80%
Vaginal pH < 4.5, Negative amine odor, absent or scant PMNs
Treatment
Fluconazole mg po (single dose)
Any of several imidazole creams or suppositories administered 3-7 days
Partner - imidazole cr. for dermatitis/balanitis

9. VAGINITIS

10. CANDIDA DERMATITIS

11. CANDIDA BALANITIS

12. TRICHOMONAS VAGINITIS
Caused by the unicellular parasite Trichomonas vaginalis
Causes 5-15% of vaginitis in STD clinics
Sexually transmitted - (Older women - delayed diagnosis of chronic infection)
Colonizes male urethra - mostly asymptomatic but can cause NGU

13. TRICHOMONAS VAGINITIS
Symptoms
Increased vaginal discharge, often profuse
Sometimes malodor
Vulvar irritation, pruritis
Physical Examination
Homogeneous discharge, yellow, copious
Mucosal erythema, petechiael cervix (strawberry cervix), bubbles in vaginal fluid

14. TRICHOMONAS VAGINITIS
Diagnosis
Motile trichomonads and predominant PMNs on saline wet prep
Vaginal pH > 5.0, Positive amine odor
Treatment
Metronidazole 2.0 gm (single dose)
Metronidazole 500 mg po bid for 7 days if single dose fails
Partner - Eval. and Metro. 2.0 gm po (single dose)

15. TRICHOMONAS VAGINITIS

16. TRICHOMONAS VAGINALIS

17. WHAT IS BACTERIAL VAGINOSIS?
Most prevalent cause of vaginal symptoms in women of childbearing age
Characterized by:
Increased malodorous discharge
Decrease or absence of Lactobacillus sp. (L. crispatus and L. jensenii most common)
Overgrowth of Gardnerella vaginalis, Mycoplasma sp. and other anaerobic organisms
Altered pattern of organic acids from these bacteria (e.g., putrescine, cadaverine, etc.) producing odor
Lack of inflammation – vaginosis (not vaginitis)

18. HISTORY OF BACTERIAL VAGINOSIS
1892 – Doderlein described normal vaginal bacteria in pregnant women – Later became known as Lactobacillus
1899 – Menge and Kronig isolated facultative and strictly anaerobic bacteria, as well as the Doderlein bacillus from the vaginal bacteria of most women
Early Studies – Established the normal flora of women – Lactobacillus sp. and a mixture of other organisms

19. HISTORY OF BACTERIAL VAGINOSIS
Early 1900’s – “Leukorrhea” – white discharge from the vagina became focus of research
Initially thought to have come from the uterus
Treated by curettage of the endometrium
1913 – A. H. Curtis demonstrated the bacteria that later became known as Gardnerella
1913 – Curtis also demonstrated:
a. The discharge was of vaginal origin, not endometrial
b. Women with leukorrhea did not have many Dordelein bacilli
c. Presence of anaerobic bacteria correlated with leukorrhea

20. HISTORY OF BACTERIAL VAGINOSIS
1920’s – R. Schroder reported 3 types of vaginal flora
1. Acid-producing rods – Doderlein’s bacilli – and the least pathogenic flora
2. Mixed flora with Doderlein bacilli in the minority
3. Mixed vaginal flora with no Doderlein bacilli and the most pathogenic flora
1950 – J.D. Weaver also noted the association of mixed flora with BV

21. HISTORY OF BACTERIAL VAGINOSIS
1955 – Gardner and Dukes demonstrated that Haemophilus vaginalis caused non-specific vaginitis (Later named Gardnerella vaginalis)
1955 – Gardner and Dukes erroneously failed to find association with mixed flora
For 25 years research focused on Gardnerella vaginalis as the cause of BV and ignored the potential role of other organisms.

22. WHAT’S IN A NAME? Leukorrhea Non-specific vaginitis
Haemophilus vaginalis vaginitis
Gardnerella vaginitis
Anaerobic vaginosis (but not just anaerobes)
Bacterial vaginosis (since inflammation is not a feature of BV, the term vaginosis has replaced vaginitis)

23. EPIDEMIOLOGY Prevalence depends upon population studied
Student Health Clinics – 4-10%
Family Planning Clinics – 17-19%
Pregnant women – 16-29%
Infertility Clinics – 30%
STD Clinics – 24-40%

24. EPIDEMIOLOGY Prevalence also depends on ethnicity
Large U.S. Study of pregnant women
13,747 at weeks gestation
16.3% of women had BV
Asians – 6.1%
Caucasians – 8.8%
Hispanics – 15.9%
African American – 22.7%
51% of 4,718 women in Ugandan study

25. EPIDEMIOLOGY BV is common in most populations
More common in STD clinics than in family planning or prenatal clinics
More common in women with discharge
Related to ethnicity for unknown reasons
Especially common in Sub-Saharan Africa

26. WHAT ABOUT SEXUAL TRANSMISSION?
Conflicting and controversial area
Women who use condoms have decreased prevalence of BV
Yet multiple partner treatment trials have failed to demonstrate benefit to women with BV
Evidence of sexual transmission of BV in women who have sex with women

27. WHAT ABOUT SEXUAL TRANSMISSION?
Females with no sexual exposure have significantly lower prevalence of BV
Some studies have found association with younger age of sexual debut
In college women, Amsel demonstrated that 0 of 18 virgins versus 69 of 293 (24%) sexually experienced women had BV

28. WHAT ABOUT SEXUAL TRANSMISSION?
Association with number of partners also seen
Women with new or multiple sex partners also have higher prevalence of BV
Evidence of NGU in male partners of patients with BV

29. WHAT ABOUT SEXUAL TRANSMISSION?
Sexual transmission of Gardnerella vaginalis has been demonstrated
Gardner and Pheifer detected G. vaginalis in the urethras of 79 and 86% of male sex partners of women with BV but not in controls
Piot et al. developed a typing system and demonstrated that Gardnerella isolates in women with BV and from the urethras of their partners were the same
Ison and Easmon recovered G. vaginalis and other anaerobes at 103 to 107 org/ml from semen in 16% of men attending an infertility clinic

30. PREDISPOSING/RISK FACTORS
Douching
IUD as contraceptive method
Younger age
New sex partner
Multiple sex partners

31. PREDISPOSING/RISK FACTORS
Decrease or absence of Lactobacillus sp.
Non-white ethnicity
Smoking in some studies
Failure to use condoms
Female sexual partners

32. ETIOLOGY BV represents a complex change in vaginal flora
Reduction in H2O2-producing lactobacilli
Increase prevalence and concentration of G. vaginalis, M. hominis, and anaerobes such as Prevotella, Bacteroides sp., Porphyromonas, Peptostreptococcus sp., etc.
These organisms found in low levels in normal vagina – also argues against sexual transmission alone as cause

33. PATHOGENESIS
Decreased Lactobacilli – decreased lactic acid causes increased pH
Overgrowth of anaerobes associated with increased enzymes that breakdown vaginal peptides into amines that are malodorous
Trimethylamine, cadaverine, putrescine, etc.

34. PATHOGENESIS
Amines – increase vaginal transudation and squamous cell exfoliation causing the discharge
At elevated pH – G. vaginalis adheres to squamous cells (“Clue cells”)
Amines also provide substrate for growth of M. hominis

35. PATHOGENESIS
Lactobacilli are essential for normal vaginal pH and inhibit growth of other bacteria
Lactobacilli are also acidophilic and are attracted to an acid environment
Anaerobic environment of BV is not conducive to growth of lactobacilli or dominance
Remains unknown whether the loss of lactobacilli occurs first or follows the flora disturbance

36. LACTOBACILLUS INTERACTIONS
Reduction in Lactobacilli – Decreased H2O2 Production
Overgrowth of
BV-associated bacteria
Raised pH

37. CLINICAL MANIFESTATIONS
“Fishy-smelling” discharge – More noticeable after intercourse (Addition of semen with alkaline pH is similar to addition of KOH)
Discharge is gray or off-white, thin, homogeneous, and adherent to vaginal wall
No erythema or inflammation
Some patients report vaginal itching
Cervix usually normal

38. CLINICAL MANIFESTATIONS

39. CLINICAL MANIFESTATIONS
Bacterial vaginosis Trichomonas vaginitis

40. DIAGNOSIS Amsel’s Criteria (3 of 4 criteria for dx.)
Adherent, homogeneous gray-white discharge
Positive amine or whiff test with addition of 10% KOH
Elevated vaginal pH of >4.5
Presence of “clue cells” – Squamous cells with adherent bacteria (>20% of cells on wet mount)

41. DIAGNOSIS – GRAM STAIN Points Scored per Morphotype*
Bacterial Morphotype None
Large Gram-Positive Rod
Small Gram-neg/var. Rod
Curved Gm-neg/var. Rod
*Score 0-3 points – Normal
4-6 points – Intermediate
7-10 points – Bacterial Vaginosis

42. CLUE CELLS

43. COMPLICATIONS OF BV IN PREGNANCY
7 studies have reported increased risk of pre-term birth in women with BV
Relative risk from directly attributable to BV
~40% elevated risk of pre-term, low birth weight delivery
16-29% of pregnant women with BV
Large number of women at risk

44. COMPLICATIONS OF BV IN PREGNANCY
Considerable reduction in pre-term births in high risk women treated for BV
Screening and treatment is currently recommended in high-risk patients (previous pre-term delivery)
Similar results have not been seen in low-risk patients with asymptomatic BV
Therefore routine screening and treatment of BV in all asymptomatic pregnant women is not indicated

45. INFECTIOUS COMPLICATIONS OF BV
Organisms found in the lower genital tract in women with BV are found in ~50% with positive cultures of amniotic fluid or placenta
Greatly increased risk of postpartum endometritis and post-Ceasarian endometritis
Increased rates of wound infections

46. INFECTIOUS COMPLICATIONS OF BV
Vaginal cuff cellulitis after hysterectomy
Post-abortion PID
Pre-operative antibiotic prophylaxis that covers BV-associated flora can reduce these complications
Since the 1970’s BV has also been associated with PID, especially in the absence of GC or CT

47. BV AND HIV ASSOCIATION
Presence of BV or absence of lactobacilli associated with heterosexual transmission of HIV
2-fold increased prevalence of HIV in Thai and Ugandan women with BV
Study of African pregnant and postnatal women in Malawi found that women with BV were more likely to seroconvert to HIV
These data raise the question of whether BV should be treated more aggressively (In the past – asymptomatic BV was not treated)

48. TREATMENT OF BV Treatment Metronidazole 500 mg po bid for 7 d
Metronidazole 2.0 gm no longer recommended
Metro. 0.75% gel qd or bid for 5 d
Clinda 2% Cr., 5 gm qd for 7 d
Clinda 300 mg po bid for 7d (Active against Lactobacillus - interferes with re-establishment of normal flora
Partner tx. - No treatment required
New Drug - Tinidazole 500 bid po x 5 days – 95% efficacy/ Vaginally once daily – 80% eff.

49. SIDE EFFECTS OF TREATMENT
Overall in about 15% of patients
Nausea
Metallic taste
Headaches
Gastrointestinal complaints
Oral metronidazole assoc. with Disulfiram-like or “antabuse” reaction after consumption of alcohol – Patient education point
3-5% will stop therapy due to side-effects

50. RECURRENT BV 80-90% cure rates at 1 week 15-30% recur within 3 months
Single Dose versus 7 day course – 73% vs. 82%
Higher recurrence rates for single dose tx.

51. RECURRENT BV
Several trials have demonstrated that partner treatment does not improve clinical outcome of BV or reduce recurrence
Discrepancy between data suggesting sexual transmission and lack of benefit with treatment of male partners is puzzling
Excellent opportunities for further research

52. RECURRENT BV – COMBINED OR ALTERNATIVE TREATMENTS
Reduction in Lactobacilli – Decreased H2O2 Production
Replace
Lactobacilli
Oral or vag
Overgrowth of
BV-associated bacteria
Raised pH
Maintain
4.5 pH – vag. gel
Intermittent Tx.

53. RECURRENT BV – COMBINED OR ALTERNATIVE TREATMENTS
Replacement or Restoration of Lactobacilli (LB)(Bacteriotherapy)
Unfortunately lack of efficacy with few controlled trials
LB used needs to be able to adhere and produce H2O2
If given orally, LB needs to survive pass through GI tract and ascend from the perianal area into the vaginal area
Lactobacilli used have not been vaginal strains

54. RECURRENT BV – COMBINED OR ALTERNATIVE TREATMENTS
Lactobacilli in yogurt strains do not bind to vaginal epithelial cells
Only 1 of 14 women were cured after applying yogurt intravaginally twice daily for 7 days
Little utility for therapies employing yogurt

55. RECURRENT BV – COMBINED OR ALTERNATIVE TREATMENTS
Other types of capsules, powders, etc. in health food stores are also dairy derived
In addition, 9 of 16 preparations were contaminated with other types of bacteria and 5 of 16 did not contain peroxide producing strains
Placebo-controlled trial of purified Lactobacillus suppositories being studied by Sharon Hillier.
~50% of women improved during therapy
Only 4 of 29 remained free of BV at 2nd visit

56. RECURRENT BV – COMBINED OR ALTERNATIVE TREATMENTS
Disinfectants
Chlorhexidine – 79% effective but 50% recurred at one month
Povidone-iodine – bid for 2 wks – only 20 % efficacy
Acidifiers
Lactic Acid suppository – 20% efficacy
Lactic acid gel x 7 days – 77% - 7 day follow-up – not repeated
5% acetic acid tampon – 38% efficacy
Suppressive therapy – Currently being studied (Sobel)
Metronidazole or Tinidazole twice a week
Results pending

57. WHAT CAN WE OFFER PATIENTS WITH RECURRENT BV?
Clearly explain bacterial vaginosis
Carefully go through personal hygiene practices to remove douching, etc. that may disrupt normal flora
Explain that course of therapy may relieve symptoms but it takes time for the bacterial imbalance normalize and recolonize with Lactobacilli
Longer course of antibiotics or combination therapy for recurrences (2 weeks/ oral + vaginal therapy)
???Suppressive and alternative combination therapy in the future