MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS
Vaginal discharge
Phillip Hay
Abstract
Vaginal discharge is a common presentation in sexual health clinics,
gynaecology clinics and general practice. The three common causes
with vaginal pathology e candidiasis, bacterial vaginosis and trichomo-
niasis e are diagnosed with the aid of relatively simple diagnostic tests.
Cervicitis caused by organisms such as Chlamydia can cause a purulent
discharge. Other causes include atrophic vaginitis, desquamative in-
flammatory vaginitis, cytolytic vaginosis and rarely neoplasia. Candidi-
asis is treated initially with oral or topical azoles. Bacterial vaginosis and
trichomoniasis are treated with metronidazole, and partner notification
is required for the latter. Frequently recurrent candidiasis and bacterial
vaginosis are problematic, and specialist advice should be sought.
Keywords Bacterial vaginosis; MRCP; trichomoniasis; vaginal
candidiasis; vaginal discharge; vaginal microscopy
Introduction
Vaginal discharge is a common presentation, and most women
develop an abnormal discharge at some point in their life.
Symptoms can be concealed because of embarrassment, so
sensitivity is needed when taking a history. A few have frequent
recurrences, and the condition can come to dominate their lives.
Important questions for the history are shown in Table 1.
The diagnosis can readily be confirmed by microscopy and
culture of appropriate swabs. It is important for practitioners to
have an understanding of normal physiology, changes with age
and pathological conditions. The two most common causes of
abnormal discharge e candidiasis and bacterial vaginosis (BV) e
are not regarded as sexually transmitted, whereas trichomoniasis
and cervicitis are.
Physiology
In pre-menarcheal girls, the vagina is lined with a simple cuboidal
epithelium. The pH is neutral, and the epithelium is colonized
with skin commensals. Under the influence of oestrogen at pu-
berty, stratified squamous epithelium develops and lactobacilli
become the predominant organism. The pH falls to 3.5e4.5. After
the menopause, atrophic changes occur, with a return to flora
more similar to those of the skin. The pH again rises to 7.0.
Physiological discharge
Normal vaginal discharge is white or yellowish. It consists of
epithelial cells, mucus, bacteria and fluid transudate. Lactic acid
Phillip Hay MBBS FRCP is Reader and Honorary Consultant HIV
Medicine Decommissioned Consultant in Sexual Health at St George’s
University Hospitals NHS Foundation Trust, UK. Competing interests:
within the last five years, Dr. Hay has received payment for advice,
speaking at meetings and attendance at conferences from Bayer
Consumer Healthcare, Hologic, Becton-Dickinson.
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Key Points
C Vaginal discharge can be diagnosed clinically, supported by
microscopy, culture and nucleic acid amplification tests
C Uncomplicated candidiasis and bacterial vaginosis are readily
treated with oral or topical azoles and metronidazole,
respectively
C Cervicitis associated with gonorrhoea, chlamydia or Myco-
plasma genitalium can present as discharge
C Less common causes include desquamative inflammatory
vaginitis, cytolytic vaginosis and cervical ectropion
C Recurrent vaginal discharge is best managed through
specialist referral
comes from glycogen being metabolized by vaginal epithelium
and lactic-acid-producing bacteria e lactobacilli or bifidobac-
teria. Physiological discharge increases mid-cycle. It also in-
creases in pregnancy and sometimes when women start a
combined oral contraceptive pill. Cervical ectropion can be
associated with excess mucus production causing persistent
discharge, which can be treated by cervical cautery.
Abnormal discharge
Vaginal discharge can originate from anywhere in the upper or
lower genital tract. Discharge arising from the vagina itself can be
physiological or pathological (Table 1). Uncommon causes are
summarized in Table 2.
The key points in history-taking are:
! a standard sexual history, as described in other chapters
! the characteristics of the discharge: colour, consistency,
amount (use of pads or tampons), smell and whether it is
bloodstained
! associated symptoms such as dyspareunia, either superfi-
cial or deep, itching or soreness
! whether there have been similar occurrences, whether
there were trigger factors, and the relationship to the
menstrual cycle
! self-treatment, previous treatments and response to them,
and recent antibiotic use
! washing practices, douching and antiseptics.
Diagnostic tests
In specialized sexual health clinics candidiasis, BV and tricho-
moniasis can be diagnosed by microscopy of a saline wet mount
and a Gram-stained vaginal smear. This allows immediate diag-
nosis, subsequently supported by laboratory culture and nucleic
acid detection tests as needed. In the absence of microscopy,
vaginal pH can be measured simply with narrow-range pH paper.
BV and trichomoniasis are excluded by a pH <4.5, but a pH >4.5
is not very specific for a positive diagnosis.
1 ! 2018 Published by Elsevier Ltd.
 MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS

Differential diagnosis of the principal causes of abnormal vaginal discharge

Symptoms and signs Candidiasis Bacterial vaginosis Trichomoniasis Cervicitis

Itching or soreness þþ e þþþ e

Smell May be ‘yeasty’ Offensive, fishy May be offensive e
Colour White White or yellow Yellow or green White or green
Consistency Curdy Thin, homogenous Thin, homogenous Mucoid
pH <4.5 4.5e7.0 4.5e7.0 Any
Confirmed by Microscopy and Microscopy Microscopy and NAAT test Microscopy, tests for chlamydia,
culture culture if NAAT not available gonorrhoea and Mycoplasma
genitalium

NAAT, nucleic acid amplification test.

Table 1

Other causes of abnormal vaginal discharge ! Diabetes mellitus and gliflozin-class drugs, which increase
glycosuria.
Infective conditions ! Vaginal douching, bubble baths, shower gel, tight clothing
C Upper genital tract infection, e.g. pelvic inflammatory disease, and tights.
postpartum endometritis ! Increased oestrogen:
C Primary syphilitic chancre e pregnancy
C Primary herpes e high-dose combined oral contraceptive pill.
Non-infective ! Underlying dermatosis, for example eczema.
C Desquamative inflammatory vaginitis ! Broad-spectrum antibiotic therapy.
C Atrophic vaginitis
C Cytolytic vaginosis Principal clinical features
C Retained tampon or condom ! Itching, soreness and redness of the vagina and vulva.
C Cervical ectropion or endocervical polyp ! Curdy white discharge that can smell yeasty but not
C Intrauterine contraceptive device unpleasant.
C Allergic vaginitis, chemical irritation ! Sometimes fissuring and excoriations.
C Physical trauma Not all candidiasis presents in the same way; in some cases,
C Fistula: rectovaginal or vesicovaginal particularly with non-albicans strains, there can be itching and
C Vault granulation tissue redness with a thin watery discharge. The diagnosis can be
C Neoplasia confirmed by microscopy and culture of the vaginal fluid.
Asymptomatic women from whom Candida is grown on culture
Table 2 do not require treatment.

Nucleic acid amplification tests (NAATs) are also performed
for gonorrhoea and chlamydia, as discussed in other chapters.
NAAT tests for Mycoplasma genitalium and Trichomonas are
increasingly being performed: the sensitivity of microscopy for
Trichomonas is <50% compared with NAAT testing.
Vaginal candidiasis
Over three-quarters of women have at least one episode of
vaginal candidiasis in their lifetime. At any point, 25% women
have candidal colonization of the vagina, but only a minority get
symptoms. Candida albicans is found in >80% cases. Sexual
acquisition is rarely important, although intercourse is an
established risk factor: the physical trauma of intercourse can
trigger an episode. It is oestrogen-dependent so rarely seen in
prepubertal girls or postmenopausal women. The invasiveness of
C. albicans is increased by oestrogen.
Predisposing factors for candidiasis
! Immunosuppressive therapy, for example corticosteroids.
Treatment
Licensed treatments produce cure rates of 80e95% in non-
pregnant women. Some women have a preference for oral
therapy, particularly if required at the time of menstruation.
Vaginal creams and pessaries can be prescribed in a variety of
doses and duration of treatment. Commonly prescribed treat-
ments are:
! a single dose of a topical azole, for example a clotrimazole
pessary 500 mg in a single dose
! oral fluconazole 150 mg tablet as a single dose.
Longer courses of treatment, for example clotrimazole 100 mg
daily for 6e7 days, are indicated:
! in pregnancy
! when there are predisposing factors that cannot be elimi-
nated, such as corticosteroid therapy
! for women with frequent recurrences.
Complications and pregnancy
Oral azoles are not recommended in pregnancy because of
teratogenicity.

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 MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS
Complications are uncommon. Women occasionally become
allergic to topical agents after regular application. In some
women, a severe episode of candidiasis can trigger long-term
vulvodynia.
Symptomatic candidal infection of male partners is uncom-
mon, but they sometimes react to candidal antigens, developing
soreness and balanitis after intercourse.
Persistent or recurrent candidiasis
Recurrent Candida infection and Candida not responding to
treatment are uncommon. Individuals presenting as ‘treatment-
resistant candidiasis’ usually have an alternative diagnosis such
as herpes simplex, vulvodynia or a dermatological condition
such as eczema or lichen sclerosus.
Genuine recurrent Candida can be suppressed by various
regimens such as weekly fluconazole 150 mg for 6 months.1
Unfortunately, this does not prevent further recurrences, and
treatment may need to be continued for longer.
If resistance to treatment is shown clinically and in vitro,
referral to a specialist clinic is advised; here new antifungal
agents such as voriconazole may be used, or unlicensed boric
acid applied intravaginally.
Bacterial vaginosis
BV is the most common cause of abnormal vaginal discharge in
women of childbearing age. Studies in antenatal and gynaecology
clinics show a prevalence of approximately 12% in the UK. The
reported prevalence has varied widely from as low as 5% in a
selected group of asymptomatic college students to 50% of
women in a large study in rural Uganda. It is more common in
black women and women who have an intrauterine contracep-
tive device in place. It is also more common in women with
sexually transmitted infections but has been reported in virgins,
and may be particularly common in lesbian women. The condi-
tion often arises spontaneously around the time of menstruation
and can resolve mid-cycle.
When BV develops, predominantly anaerobic organisms in-
crease in concentration up to a thousand-fold and overwhelm the
lactobacilli (Figure 1). Vaginal pH rises to between 4.5 and 7.0.
Figure 1 Phase contrast microscopy of vaginal fluid at #400 magni-
fication. Trichomonas vaginalis is seen as an ovoid or pear-shaped
organism with four anterior flagellae (arrows).
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The bacteria most often found by culture are Gardnerella vagi-
nalis, Prevotella spp., Mycoplasma hominis and Mobiluncus spp.
Molecular techniques have more recently found Atopobium
vaginae, BV-associated bacteria (BVAB1eBVAB3: Clostridiales),
Megasphaera, Sneathia and Leptotrichia. Additionally, a biofilm
consisting predominantly of Gardnerella and A. vaginae has been
described, which places these organisms at the centre of
pathogenesis.
Clinical features
! Offensive fishy-smelling discharge.
! Discharge that is characteristically thin and homogenous,
and adheres to the walls of the vagina.
! White or yellow discharge.
! A smell that is particularly noticeable around the time of
menstruation or after intercourse. Semen itself can give off
a weak fishy smell.
The diagnosis was traditionally made in clinical practice
identifying at least three of the composite (Amsel) criteria:
! vaginal pH >4.5
! release of a fishy smell on addition of alkali (10% potas-
sium hydroxide)
! a characteristic discharge on examination
! the presence of ‘clue cells’ on microscopy.
Clue cells are vaginal epithelial cells so heavily coated with
bacteria that the border is obscured (Figure 2). In sexual health
clinics, BV is now diagnosed from a Gram-stained vaginal
smear. Large numbers of Gram-positive and Gram-negative
cocci are seen, with reduced or absent large Gram-positive
bacilli (Lactobacilli). Culture is not useful for diagnosis as, for
instance, Gardnerella can be grown from 50% of women who
do not have BV.
Treatment
BV resolves on treatment with antibiotics with good anti-
anaerobic activity. A comprehensive review was used to guide
the 2006 Centers for Disease Control guidelines.2 The preferred
treatment is:
! metronidazole 400 mg twice a day for 5 days.
Alternative treatments are:
! metronidazole 2 g as a single dose
! metronidazole vaginal gel 0.75% applied nightly for 5
nights
! clindamycin cream 2% applied nightly for 5e7 nights
! dequalinium chloride 10 mg pessary for 6 nights, which
has more recently been licensed in the UK.
Initial cure rates are >80%, but up to 30% of women relapse
within 1 month of treatment.
Metronidazole causes nausea and an unpleasant metallic
taste. It is best taken after food. Clindamycin cream has rarely
been associated with Clostridium difficile diarrhoea.
Complications
During pregnancy, women with BV are at greater risk of second-
trimester miscarriage and preterm delivery. This can result in
perinatal mortality or cerebral palsy. The results of studies
treating BV with metronidazole or clindamycin have been con-
flicting, so current guidelines do not recommend routine
screening and treatment.
3 ! 2018 Published by Elsevier Ltd.
 MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS

Figure 2 Microscopy of Gram-stained vaginal smears at #1000 magnification. (a) Normal flora: lactobacilli are seen as large Gram-positive rods
and there are intact epithelial cells. (b) Candidiasis: Gram-positive spores and hyphae are seen. (c) Cytolytic vaginosis: cytoplasmic debris and
isolated nuclei are seen, with lactobacilli. Occasional polymorphs are present. (d) Bacterial vaginosis: numerous small bacteria, mixed Gram-
positive and Gram-negative, including some curved rods. (All #800 magnification).

BV should be treated with metronidazole before termination
of pregnancy to reduce the subsequent incidence of endometritis
and pelvic inflammatory disease.
Recurrence
In many women, the vaginal flora is in a dynamic state, with BV
developing and remitting spontaneously. Symptomatic women
with recurrent BV can become frustrated as although the condi-
tion responds rapidly to treatment with antibiotics, it may
quickly relapse. Our inability to alter this process reflects our
current lack of knowledge of the factors that trigger BV.
Regular treatment with 0.75% metronidazole gel twice a week
for 6 months reduces the rate of recurrence.3 Some women need
simultaneous suppressive treatment for Candida.
Trichomoniasis
This sexually transmissible infection can be carried for several
months before causing symptoms. It is diagnosed in approxi-
mately 1% women attending sexual health clinics in the UK.
However, its prevalence is higher in many tropical countries,
with rates of 10e20% in some settings. In men, it is usually
asymptomatic but can present as non-gonococcal urethritis.
Clinical features
! Vulvovaginitis, which can be severe, with inflammation
sometimes extending onto the labia majora and adjacent
skin.
! Purulent, green or yellow discharge, which is sometimes
offensive.
! In many cases, additional BV.
! Sometimes punctate haemorrhages on the cervix, giving
the appearance of a ‘strawberry cervix’.
The diagnosis is traditionally confirmed by microscopy of vaginal
secretions mixed with saline, or culture in a specific medium
such as FienbergeWhittington medium. Numerous poly-
morphonuclear cells are seen, and the motile organism is iden-
tified from its shape and four moving flagella. Microscopy has a
60% sensitivity compared with culture. NAATs are now avail-
able and offer greater diagnostic sensitivity.
Management
Metronidazole is given, either 2 g as a single dose, or 400 mg
twice a day for 5 days.
Partner notification is needed, and the woman should not
resume sexual intercourse until her sexual partner(s) has been
treated. Tinidazole 2 g as a single dose is more expensive but
occasionally works when metronidazole has failed. Patients
allergic to metronidazole should be managed by desensitization,
in collaboration with an allergy specialist.
Complications and pregnancy
Trichomonas has occasionally been identified in the upper gen-
ital tract of women with pelvic inflammatory disease, but is
probably not an important cause of upper genital tract pathology.
It can be isolated from the bladder.

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 MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS
Although Trichomonas is a risk factor for preterm birth,
treating asymptomatic infection has not been shown to improve
outcome. Symptomatic women should be treated with a 5-day
course of metronidazole.
Recurrence and resistance
Persistent trichomoniasis is occasionally seen. This can be caused
by poor compliance with medication, poor absorption, reinfection
or, rarely, a resistant organism. The usual approach is to use higher
doses of metronidazole, initially 400 mg three times a day,
increasing to 1 g per rectum twice a day or intravenously. Neuro-
logical toxicity can be encountered with high doses. Some clini-
cians prescribe a broad-spectrum antibiotic such as co-amoxiclav
to eliminate bacteria such as group B streptococci that might be
metabolizing metronidazole, thereby diminishing its efficacy.
Alternative treatments are unfortunately limited and unli-
censed, but include arsphenamine pessaries, clotrimazole and
boric acid. Referral to a specialist is advised.
Cervicitis: Neisseria gonorrhoeae, Chlamydia and
M. genitalium
Cervicitis can be caused by these organisms or be non-specific in
a similar way to urethritis in men. A purulent discharge origi-
nates from the cervix, and numerous white cells are seen on
vaginal microscopy. The discharge can be white, yellow or green,
and can be bloodstained and associated with intermenstrual and
post-coital bleeding. On speculum examination, a mucopurulent
discharge may be seen coming from the cervix, and contact
bleeding after swabbing is common.
Treatment should be prescribed as for men with urethritis:
doxycycline 100 mg twice daily for 7 days, or azithromycin 1 g as
a single dose.
Vaginal discharge in children
Vaginal infections are common in childhood and usually not
related to sexual abuse. Causes include streptococcal infections
and Shigella, which can cause a chronic haemorrhagic vaginitis,
often with no history of diarrhoea. Recurrent vaginal infections
should lead to a foreign body being suspected. Pinworms
(Enterobius vermicularis) migrate from the anus at night, causing
intense irritation and inevitably scratching. The clue to the
diagnosis is the nocturnal pattern.
The cuboidal epithelium lining the vagina in children is sus-
ceptible to infection by Chlamydia or N. gonorrhoeae, which
means that if sexual abuse occurs that then leads to infection, a
generalized vaginitis with purulent discharge occurs.
Other conditions affecting the vagina
Atrophic vaginitis is common in postmenopausal women. This
can lead to superficial dyspareunia and vaginal soreness. Oes-
trogen replacement with topical oestrogen is effective. There is
an overlap with desquamative inflammatory vaginitis, a condi-
tion of unknown aetiology that also shares some features of
vaginal erosive lichen planus.
Occasionally, a true bacterial vaginitis is encountered that is
caused by a Streptococcus or other organism. This responds to
appropriate antibiotic therapy such as co-amoxiclav 375 mg three
times a day for 7 days. Toxic shock syndrome is a rare condition
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associated with retention of tampons or foreign bodies in the
vagina. An overgrowth of toxin-producing staphylococci causes
systemic shock with fever, diarrhoea, vomiting and an
erythematous rash. More frequently, a foreign body or retained
tampon merely causes an offensive BV discharge.
Cytolytic vaginosis is recognized by the cyclical nature of
irritant symptoms developing during the luteal phase of the
menstrual cycle.4 It is often initially misdiagnosed as candidiasis
that is failing to respond to treatment. On microscopy, there is
extensive cytolysis with free nuclei and cellular debris, and
polymorphs are usually absent. Treatment is with baking soda
douches, as described on the University of Virginia website.5
Self-help and over-the-counter treatments
Women should be advised to avoid douching and other washing
practices that will disturb the endogenous flora. Use of over-the-
counter Candida treatments without a confirmed diagnosis can
lead to delays in being given the correct diagnosis and treatment.
Probiotics and lactic acid gels have not been sufficiently rigorously
evaluated to allow a recommendation to be made, but some women
derive symptomatic relief from them. Anecdotally, reducing sugar
intake, stopping oestrogen-containing contraception and avoiding
tight clothing can reduce the frequency of Candida recurrences.A
KEY REFERENCES
1 Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance flucon-
azole therapy for recurrent vulvovaginal candidiasis. N Engl J Med
2004; 351: 876e83.
2 Koumans EH, Markowitz LE, Hogan V. Indications for therapy and
treatment recommendations for bacterial vaginosis in nonpregnant
and pregnant women: a synthesis of data. Clin Infect Dis 2002;
35(suppl 2): S152e72.
3 Sobel JD, Ferris D, Schwebke J, et al. Suppressive antibacterial
therapy with 0.75% metronidazole vaginal gel to prevent recurrent
bacterial vaginosis. Am J Obstet Gynecol 2006; 194: 1283e9.
4 Cibley LJ, Cibley LJ. Cytolytic vaginosis. Am J Obstet Gynecol
1991; 165: 1245e9.
5 University of Virginia Department of Student Health. https://health.
students.vcu.edu/media/student-affairs/ushs/docs/
CYTOLYTICVAGINOSIS.pdf (accessed 03 April 2018).
FURTHER READING
American Centers for Disease Control and Prevention. Sexually
transmitted diseases (STDs). http://www.cdc.gov/std/treatment/.
Brocklehurst P, Gordon A, Heatley E, Milan J. Antibiotics for treating
bacterial vaginosis in pregnancy. Cochrane Database Syst Rev
2013; 1: CD000262.
Duyebo OO, Anorlu RI, Ogunsola FT. The effects of antimicrobial
therapy on bacterial vaginosis in non-pregnant women. Cochrane
Database Syst Rev 2009; 3: CD006055.
Forna F, Gu€ lmezoglu AM. Interventions for treating trichomoniasis in
women. Cochrane Database Syst Rev 2003; 2: CD000218.
Holmes King K, Sparling PF, Stamm WE, et al., eds. Sexually trans-
mitted diseases. 4th edn. New York: McGraw Hill; 2007.
USEFUL WEBSITES
British Association for Sexual Health and HIV: http://www.bashh.org.uk.
Royal College of Obstetrics and Gynaecology: http://www.rcog.org.uk.
5 ! 2018 Published by Elsevier Ltd.
 MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS

TEST YOURSELF
To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the
end of the issue or online here.

Question 1 What is the most appropriate treatment?

A 29-year-old woman presented with abnormal vaginal
discharge. She had a history of metronidazole allergy with rash,
facial oedema and tightness in the throat.
Investigation
! Wet-mount examination showed motile Trichomonas
vaginalis
What is the best management plan?
A. Tinidazole 2 g single dose orally
B. Clotrimazole pessaries 100 mg at night for 6 days
C. A course of desensitization followed by metronidazole 400
mg 12-hourly for 5 days
D. Co-amoxiclav 625 mg 8-hourly daily for 5 days
E. She should be told that she cannot be treated safely but it
should resolve within 6 months
Question 2
A 26-year-old woman presented with vaginal itching, soreness
and discharge at 18 weeks’ gestation in her first pregnancy. She
was found to have candidiasis.
A. Clotrimazole 500 mg pessary, single dose
B. Fluconazole 150 mg orally, single dose
C. Nystatin pessaries 100,000 IU at night for 6 days
D. Clotrimazole pessaries 100 mg at night for 6 days
E. Fluconazole 100 mg at night for 6 days
Question 3
A 16-year-old woman presented with a 1-week history of an
offensive thin discharge that had started at the end of
menstruation.
Which of the following findings is not a criterion for a diag-
nosis of bacterial vaginosis?
A. Vaginal pH of 5.5
B. Clue cells seen on wet-mount microscopy
C. Numerous polymorphonuclear cells seen on wet-mount
microscopy
D. Replacement of lactobacilli with numerous Gram-positive
and Gram-negative bacteria on Gram staining
E. Release of a fishy odour on mixing of vaginal fluid with
10% potassium hydroxide

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