Transcript ETIOLOGY OF NGU

DIAGNOSIS AND TREATMENT
OF VAGINITIS
Stephanie N. Taylor, MD
LSUHSC Department of Medicine
Section of Infectious Diseases
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.
VAGINITIS

Inflammation of the vagina leading to
vaginal irritation and discharge
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Both cervicitis and vaginitis can cause
vaginal discharge and distinction can be
difficult (Speculum Exam)
ETIOLOGY OF VAGINITIS
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YEAST (CANDIDA SP.)
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TRICHOMONAS VAGINALIS
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BACTERIAL VAGINOSIS
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ALLERGIC RXN, ESTROGEN DEF., etc.
VULVOVAGINAL CANDIDIASIS
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Candida albicans, Candida glabrata, etc.
colonize vagina
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Proliferation or allergic reaction caused
by known and unknown factors
(Antibiotic use, diabetes, pregnancy, etc.)
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Estimated that >75% of women will have
at least one episode during lifetime
VULVOVAGINAL CANDIDIASIS

VVC causes 20-25% of vaginitis in STD
clinics
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Not truly sexually transmitted - males
can acquire the organism however
(Candida balanitis or dermatitis)
VULVOVAGINAL CANDIDIASIS
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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
VULVOVAGINAL CANDIDIASIS

Diagnosis
 KOH
Prep - Pseudohyphae in ~80%
 Vaginal pH < 4.5, Negative amine odor,
absent or scant PMNs

Treatment
 Fluconazole
150-200 mg po (single dose)
 Any of several imidazole creams or
suppositories administered 3-7 days
 Partner - imidazole cr. for dermatitis/balanitis
VAGINITIS
CANDIDA DERMATITIS
CANDIDA BALANITIS
TRICHOMONAS VAGINITIS

Caused by the unicellular parasite
Trichomonas vaginalis
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Causes 5-15% of vaginitis in STD clinics
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Sexually transmitted - (Older women delayed diagnosis of chronic infection)
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Colonizes male urethra - mostly
asymptomatic but can cause NGU
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
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)
TRICHOMONAS VAGINITIS
TRICHOMONAS VAGINALIS
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)
HISTORY OF BACTERIAL VAGINOSIS

1892 – Doderlein described normal vaginal
bacteria in pregnant women – Later
became known as Lactobacillus
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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
HISTORY OF BACTERIAL VAGINOSIS
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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
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
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.
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)
EPIDEMIOLOGY

Prevalence depends upon population studied

Student Health Clinics – 4-10%

Family Planning Clinics – 17-19%

Pregnant women – 16-29%
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Infertility Clinics – 30%

STD Clinics – 24-40%
EPIDEMIOLOGY
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Prevalence also depends on ethnicity
Large U.S. Study of pregnant women
13,747 at 23-26 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
EPIDEMIOLOGY

BV is common in most populations
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More common in STD clinics than in family
planning or prenatal clinics
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More common in women with discharge

Related to ethnicity for unknown reasons
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Especially common in Sub-Saharan Africa
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
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Evidence of sexual transmission of BV in
women who have sex with women
WHAT ABOUT SEXUAL TRANSMISSION?

Females with no sexual exposure have
significantly lower prevalence of BV
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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
WHAT ABOUT SEXUAL TRANSMISSION?
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Association with number of partners also seen
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Women with new or multiple sex partners also
have higher prevalence of BV
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Evidence of NGU in male partners of patients
with BV
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
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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
PREDISPOSING/RISK FACTORS

Douching

IUD as contraceptive method

Younger age
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New sex partner
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Multiple sex partners
PREDISPOSING/RISK FACTORS
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Decrease or absence of Lactobacillus sp.
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Non-white ethnicity
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Smoking in some studies
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Failure to use condoms
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Female sexual partners
ETIOLOGY
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BV represents a complex change in vaginal flora
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Reduction in H2O2-producing lactobacilli
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Increase prevalence and concentration of G. vaginalis,
M. hominis, and anaerobes such as Prevotella,
Bacteroides sp., Porphyromonas, Peptostreptococcus sp.,
etc.
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These organisms found in low levels in normal vagina –
also argues against sexual transmission alone as cause
PATHOGENESIS
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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.
PATHOGENESIS

Amines – increase vaginal transudation and squamous
cell exfoliation causing the discharge
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At elevated pH – G. vaginalis adheres to squamous cells
(“Clue cells”)
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Amines also provide substrate for growth of M. hominis
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
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Anaerobic environment of BV is not conducive to
growth of lactobacilli or dominance
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Remains unknown whether the loss of lactobacilli
occurs first or follows the flora disturbance
LACTOBACILLUS INTERACTIONS
Reduction in Lactobacilli –
Decreased H2O2 Production
Overgrowth of
BV-associated bacteria
Raised pH
CLINICAL MANIFESTATIONS

“Fishy-smelling” discharge – More noticeable after
intercourse (Addition of semen with alkaline pH is similar to
addition of KOH)
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Discharge is gray or off-white, thin, homogeneous, and
adherent to vaginal wall
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No erythema or inflammation
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Some patients report vaginal itching
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Cervix usually normal
CLINICAL MANIFESTATIONS
CLINICAL MANIFESTATIONS
Bacterial vaginosis
Trichomonas vaginitis
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)
DIAGNOSIS – GRAM STAIN
Bacterial Morphotype
Points Scored per Morphotype*
None 1+
2+
3+
4+
Large Gram-Positive Rod 4
3
2
1
0
Small Gram-neg/var. Rod
0
1
2
3
4
Curved Gm-neg/var. Rod
0
1
2
3
4
*Score 0-3 points – Normal
4-6 points – Intermediate
7-10 points – Bacterial Vaginosis
CLUE CELLS
COMPLICATIONS OF BV IN
PREGNANCY
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7 studies have reported increased risk of preterm birth in women with BV
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Relative risk from 2.0-6.9 directly attributable
to BV
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~40% elevated risk of pre-term, low birth
weight delivery
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16-29% of pregnant women with BV
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Large number of women at risk
COMPLICATIONS OF BV IN
PREGNANCY
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Considerable reduction in pre-term births in high risk
women treated for BV
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Screening and treatment is currently recommended in
high-risk patients (previous pre-term delivery)
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Similar results have not been seen in low-risk patients
with asymptomatic BV
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Therefore routine screening and treatment of BV in all
asymptomatic pregnant women is not indicated
INFECTIOUS COMPLICATIONS OF BV
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Organisms found in the lower genital tract in
women with BV are found in ~50% with
positive cultures of amniotic fluid or placenta
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Greatly increased risk of postpartum
endometritis and post-Ceasarian endometritis
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Increased rates of wound infections
INFECTIOUS COMPLICATIONS OF BV
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Vaginal cuff cellulitis after hysterectomy
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Post-abortion PID
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Pre-operative antibiotic prophylaxis that
covers BV-associated flora can reduce these
complications
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Since the 1970’s BV has also been associated
with PID, especially in the absence of GC or
CT
BV AND HIV ASSOCIATION
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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
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Study of African pregnant and postnatal women in Malawi
found that women with BV were more likely to seroconvert
to HIV
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These data raise the question of whether BV should be
treated more aggressively (In the past – asymptomatic BV
was not treated)
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.
SIDE EFFECTS OF TREATMENT
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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
RECURRENT BV
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80-90% cure rates at 1 week
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15-30% recur within 3 months
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Single Dose versus 7 day course – 73% vs. 82%
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Higher recurrence rates for single dose tx.
RECURRENT BV
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Several trials have demonstrated that partner
treatment does not improve clinical outcome of
BV or reduce recurrence
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Discrepancy between data suggesting sexual
transmission and lack of benefit with treatment
of male partners is puzzling

Excellent opportunities for further research
RECURRENT BV – COMBINED OR
ALTERNATIVE TREATMENTS
Replace
Lactobacilli
Oral or vag
Reduction in Lactobacilli –
Decreased H2O2 Production
Overgrowth of
BV-associated bacteria
Intermittent Tx.
Raised pH
Maintain
4.5 pH – vag. gel
RECURRENT BV – COMBINED OR
ALTERNATIVE TREATMENTS
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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
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Lactobacilli used have not been vaginal strains
RECURRENT BV – COMBINED OR
ALTERNATIVE TREATMENTS

Lactobacilli in yogurt strains do not bind to
vaginal epithelial cells
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Only 1 of 14 women were cured after applying
yogurt intravaginally twice daily for 7 days
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Little utility for therapies employing yogurt
RECURRENT BV – COMBINED OR
ALTERNATIVE TREATMENTS
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Other types of capsules, powders, etc. in health food
stores are also dairy derived
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In addition, 9 of 16 preparations were contaminated
with other types of bacteria and 5 of 16 did not contain
peroxide producing strains
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Placebo-controlled trial of purified Lactobacillus
suppositories being studied by Sharon Hillier.
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~50% of women improved during therapy
Only 4 of 29 remained free of BV at 2nd visit
RECURRENT BV – COMBINED OR
ALTERNATIVE TREATMENTS
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Disinfectants
 Chlorhexidine – 79% effective but 50% recurred at one month
 Povidone-iodine – bid for 2 wks – only 20 % efficacy
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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
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