Management of Genital Ulcers and Discharges

Transcription

Management of
Genital Ulcers
and Discharges
MOH Clinical Practice Guidelines 1/2009
Ministry of Health, Singapore
College of Medicine Building
16 College Road
Singapore 169854
TEL (65) 6325 9220
FAX (65) 6224 1677
WEB www.moh.gov.sg
ISBN 978-981-08-3340-4
Academy of
Medicine,
Singapore
Chapter of Dermatologists
College of Physicians,
Singapore
College of Obstetricians
and Gynaecologists,
Singapore
College of Family
Obstetrical &
Physicians,
Gynaecological
Singapore
Society of Singapore
Dermatological
Society of
Singapore
May 2009
Levels
evidence
and
grades
recommendation
Levels
ofof
evidence
and
grades
ofof
recommendation
Levels of evidence
Level
Level
1++ ++
+
1+
-
1
2++ ++
+
2+
-
2
Type
Type of
of Evidence
Evidence
High quality meta-analyses, systematic reviews of randomised
controlled trials (RCTs), or RCTs with a very low risk of bias.
Well-conducted meta-analyses, systematic reviews of RCTs, or
RCTs with a low risk of bias.
Meta-analyses, systematic reviews of RCTs, or RCTs with a high
risk of bias
High quality systematic reviews of case control or cohort studies.
High quality case control or cohort studies with a very low risk of
confounding or bias and a high probability that the relationship is
causal
Well conducted case control or cohort studies with a low risk of
confounding or bias and a moderate probability that the relationship
is causal
Case control or cohort studies with a high risk of confounding or
bias and a significant risk that the relationship is not causal
3
Non-analytic studies, e.g. case reports, case series
4
Expert opinion
Grades of recommendation
Grade
Grade
A
Recommendation
Recommendation
At least one meta-analysis, systematic review of RCTs, or
++
RCT rated as 1+ + and directly applicable to the target
population; or
A body of evidence consisting principally of studies rated as
1++, directly applicable to the target population, and
demonstrating overall consistency of results
B
++
A body of evidence including studies rated as 2++, directly
applicable to the target population, and demonstrating
overall consistency of results; or
++
+
Extrapolated evidence from studies rated as 1+ + or 1+
A body of evidence including studies rated as 2++, directly
applicable to the target population and demonstrating overall
consistency of results; or
Extrapolated evidence from studies rated as 2++ ++
Evidence level 3 or 4; or
D
Extrapolated evidence from studies rated as 2++
Recommended best practice based on the clinical experience
GPP
(good practice points) of the guideline development group.
C
1
CLINICAL PRACTICE GUIDELINES
Management of Genital Ulcers
and Discharges
2
Published by Ministry of Health, Singapore
16 College Road,
Singapore 169854
Printed by Golden City Colour Printing Co. (Pte) Ltd
Copyright © 2009 by Ministry of Health, Singapore
ISBN 978-981-08-3340-4
Available on the MOH website: http://www.moh.gov.sg/cpg
Statement of Intent
These guidelines are not intended to serve as a standard of medical care.
Standards of medical care are determined on the basis of all clinical data
available for an individual case and are subject to change as scientific
knowledge advances and patterns of care evolve.
The contents of this publication are guidelines to clinical practice, based on
the best available evidence at the time of development. Adherence to these
guidelines may not ensure a successful outcome in every case. These
guidelines should neither be construed as including all proper methods of
care, nor exclude other acceptable methods of care. Each physician is
ultimately responsible for the management of his/her unique patient, in the
light of the clinical data presented by the patient and the diagnostic and
treatment options available.
Contents
Page
Executive summary of recommendations
1
1
Introduction
25
2
Management of genital ulcers
26
3
Management of genital discharges
42
4
Cost-effectiveness issues
71
5
Clinical quality improvement
72
References
73
Self-assessment (MCQs)
90
Workgroup members
95
4
Foreword
Sexually transmitted infections (STIs) remain a public health problem of major
significance in most parts of the world. Infection with STIs can lead to acute
symptoms, chronic infection and serious delayed consequences such as
infertility, ectopic pregnancy and cervical cancer. There has been an increasing
trend in the overall STI incidence in Singapore for the past ten years, from 160
cases per 100,000 population in 1998 to 251 cases per 100,000 population in
2007.
Genital ulcers and genital discharge are commonly seen symptoms of STIs.
The incidence of genital ulcer disease is on the rise in Singapore and the two
commonest causes are genital herpes and primary syphilis. In patients
presenting with a urethral discharge, gonorrhoea and Chlamydia trachomatis
infections are the most common causes in Singapore.
Primary care doctors are often the first contact point for patients with genital
ulcers or discharges. According to the results of a survey on STI management
practices among GPs in 2006 and 2007, it was found that the overall medical
management of STI by primary care physicians was acceptable. However,
there was variation in terms of medications and ordering relevant investigations
for their patients. It is therefore timely to develop this first national guideline
that incorporates the best available evidence from the scientific literature, to
assist our doctors in the management of genital ulcers and discharge.
PROFESSOR K SATKU
DIRECTOR OF MEDICAL SERVICES
5
Executive summary of recommendations
Details of recommendations can be found in the main text at the pages indicated.
Management of genital ulcers
D It is recommended that the following diagnostic approach be taken in
any patient with genital ulcers or discharges (pg 27):
A. Patient history:
1. Lesion history: prodrome, initial presentation (especially
presence of vesicles), duration of lesion, pain, symptoms of
urethritis, other systemic symptoms, use of systemic or topical
remedies, any history of similar symptoms in the past or partners
with similar symptoms.
2. Medical history: HIV status, skin conditions, drug allergies, and
medications.
3. Sexual history: gender of partners, number of partners, venue for
meeting partners, commercial sex exposure, partners with
symptoms or signs, partners with known HSV or recent syphilis
diagnosis.
4. Travel history: geographical area where sexual intercourse has
taken place.
B. Physical exam:
1. Lesion: examine for appearance, distribution, number, size,
induration, depth, and tenderness.
2. Genital exam: examine genital and perianal area for other lesions.
3. Lymph node(s): note number and location of enlarged nodes,
size, tenderness, presence of bubo.
4. General exam: thorough examination of oral cavity and skin of
torso, palms and soles. In patients with syphilis, this would
include an examination of the cardiovascular and neurological
systems.
Grade D, Level 4
A A diagnosis based only on the patient’s medical history and physical
examination frequently may be inaccurate. Ideally, all patients who have
genital ulcers should be evaluated with a serologic test for syphilis and a
diagnostic evaluation for genital herpes; if chancroid is suspected, the
patient should be referred to a specialist for evaluation and a test for
Haemophilus ducreyi (pg 29).
Grade A, Level 1+
1
B HIV and serologic testing for syphilis should be performed on all
patients who have STIs presenting with genital ulcers, as well as tests for
herpes simplex infection where appropriate. Locally, genital herpes and
syphilis are the two most likely infective etiologies. Non-infective causes
may need to be considered (pg 29).
Grade B, Level 2++
B The clinician should treat for the diagnosis considered most likely, on
the basis of clinical presentation and epidemiologic circumstances. In
some instances, treatment must be initiated for additional conditions
because of diagnostic uncertainty (pg 29).
Grade B, Level 2++
GPP Successful management of STI-associated syndromes requires that
staff are respectful of patients and are not judgmental. Examination must
be done in appropriate surroundings where privacy can be ensured and
confidentiality guaranteed. Patients should be educated and counseled on
their condition as well as safer sex (pg 29).
GPP
Management of herpes simplex virus (HSV) infection
B In performing serology for HSV infection, assays that detect the typespecific glycoproteins gG1 (HSV 1) and gG2 (HSV 2) should be used
(pg 31).
Grade B, Level 2++
Treatment of first episode genital herpes (pg 32)
1.
A Acyclovir 200 mg orally 5 times daily for 5 to10 days.
Grade A, Level 1++
OR
2.
A Acyclovir 400 mg orally tid for 5 to10 days.
OR
3.
A Valacyclovir 500 mg/1g orally bid for 5 to 10 days.
Grade A, Level 1++
OR
4.
Grade A, Level 1++
B Famciclovir 250 mg orally tid for 5 to 10 days.
2
Grade B, Level 2++
C For episodic treatment of recurrent herpes, the patient should be
provided with a supply of drug or a prescription for the medication with
instructions to self-initiate treatment immediately when symptoms begin
(pg 32).
Grade C, Level 2+
Treatment of recurrent genital herpes (pg 32)
1.
A Acyclovir 200 mg orally 5 times daily or 400 mg orally tid or 800
mg orally bid for 5 days.
OR
2.
A Acyclovir 800 mg tid orally for 2 days.
OR
3.
OR
A Valacyclovir 500 mg bid for 3 days.
OR
5.
A Famciclovir 125 mg orally bid for 5 days.
OR
6.
Grade A, Level 1++
A Valacyclovir 500 mg orally bid or 1000 mg orally once a day for 5
days.
4.
Grade A, Level 1++
A Famciclovir 1 g bid orally for 1 day.
Grade A, Level 1++
Grade A, Level 1++
Grade A, Level 1++
Grade A, Level 1++
C Suppressive therapy reduces the frequency of genital herpes recurrences
and may be considered in patients who have frequent recurrences (i.e. 6 or
more recurrences per year) (pg 33).
Grade C, Level 2+
Suppressive treatment of recurrent genital herpes (pg 33)
1.
A Acyclovir 400 mg orally bid.
OR
2.
A Valacyclovir 500 mg orally od.
3
Grade A, Level 1+
Grade A, Level 1+
OR
3. A Valacyclovir 1000 mg orally od (for > 10 recurrences in 1 year).
OR
4. A Famciclovir 250 mg orally bid.
Grade A, Level 1+
Grade A, Level 1+
C Physicians should stop suppressive treatment of genital herpes after 9 to
12 months to see if recurrence occurs and continued prophylaxis is
warranted (pg 34).
Grade C, Level 2+
Treatment of genital herpes in HIV-infected patients (pg 34)
1. A Acyclovir 400 mg orally tid for 7 to 10 days.
OR
2. A Valacyclovir 1 g orally bid for 7 to 10 days.
OR
3. A Famciclovir 500 mg orally bid for 7 to 10 days.
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
Suppressive treatment of genital herpes in HIV-infected patients
(pg 34)
1. A Acyclovir 400 mg to 800 mg orally bid or tid.
Grade A, Level 1+
OR
2. A Valacyclovir 500 mg orally bid.
OR
3. A Famciclovir 500 mg orally bid.
4
Grade A, Level 1+
Grade A, Level 1+
Management of genital herpes in pregnancy
First episode genital herpes – 1st and 2nd trimester acquisition
C Management should be in line with the clinical condition with the use
of either oral or intravenous acyclovir (pg 35).
Grade C, Level 2+
C Vaginal delivery is anticipated in women who present with first episode
genital herpes in the first and second trimesters as the risk for transmission
to the neonate at delivery is low (pg 35).
Grade C, Level 2+
First episode genital herpes – 3rd trimester acquisition
C Caesarean section should be offered to all women presenting with firstepisode genital herpes lesions at the time of delivery, or within 6 weeks of
the expected date of delivery or onset of labour (pg 35).
Grade C, Level 2+
Recurrent genital herpes in pregnancy
C If there are no genital lesions at the onset of labour, Caesarean section
to prevent neonatal herpes is not indicated (pg 36).
Grade C, Level 2+
A For women with a history of recurrent genital herpes, who would opt
for caesarean delivery if HSV lesions were detected at the onset of labour,
daily suppressive acyclovir given from 36 weeks of gestation until
delivery may be given to reduce the likelihood of HSV lesions at term)
(pg 36).
Grade A, Level 1+
B Counselling for genital herpes is important and should include
(pg 36):
• Information on natural history of disease, potential for recurrent
attacks, role of asymptomatic shedding in sexual transmission
• Abstinence from sexual activity during prodromal symptoms or when
lesions are present
• Advice to inform current and new sexual partners of genital herpes
• Use of condoms with new or uninfected partners, particularly in first 12
months after first attack
5
•
•
Information on anti-viral treatment available
Risk of neonatal infection: women with a history of genital herpes or
whose partners have history of genital herpes should inform their
obstetrician early in pregnancy
Grade B, Level 2++
Management of primary syphilis
Treatment of primary syphilis (pg 37)
1. B Benzathine Penicillin G 2.4 million units i/m weekly x single dose.
(For primary syphilis, most authorities administer a single dose, while
some might use two doses for secondary syphilis).
OR
Grade B, Level 2++
2. B Aq. Procaine Penicillin G 600,000 units i/m daily x 10 days.
Grade B, Level 2++
Penicillin-allergic patients (pg 38)
1. B Doxycycline 100 mg orally bid x 14 days.
OR
2. B Erythromycin 500 mg orally qid x 14 days.
OR
3. B Azithromycin 500 mg orally od x 10 days.
Grade B, Level 2++
Grade B, Level 2++
Grade B, Level 1+
C For HIV-infected individuals, either the same treatment as in non-HIV
infected individuals or 3 doses of Benzathine Penicillin G 2.4 million units
i/m weekly are recommended (pg 38).
Grade C, Level 2+
C HIV-positive individuals with primary syphilis should be referred to an
appropriate expert for follow up (pg 38).
Grade C, Level 2+
B Oral doxycycline is the preferred oral alternative in all patients in view
of its more favourable dosing intervals and low cost (pg 38).
Grade B, Level 2++
6
GPP The treatment guidelines listed refer to management of primary
syphilis. For late latent syphilis, syphilis of unknown duration, congenital
syphilis or neurosyphilis, the treatment recommendations are different and
relevant expert advice should be sought (pg 38).
GPP
C The same quantitative nontreponemal tests [i.e rapid plasma regain
(RPR) or Venereal Disease Research Laboratory (VDRL)] should be
repeated during follow up; the DSC Clinic follows up patients for a total
period of two years (tests are repeated at 3 months; 6 months; 12 months;
18 months; 24 months) (pg 38).
Grade C, Level 2+
C A sustained fourfold or greater increase in RPR/VDRL titres suggests
re-infection or treatment failure. Following treatment of early syphilis,
RPR/VDRL should demonstrate a decrease in titre within 6 months. In
particular, patients treated with non-penicillin based regimens should be
followed up to look for signs of treatment failure (pg 38).
Grade C, Level 2+
C Since treponemal tests remain positive for life following effective
treatment, proper documentation is necessary to prevent unnecessary
retreatment. Patients should be given a letter documenting their treatment
(pg 39).
Grade C, Level 2+
D Reinfection or relapse should be retreated preferably with supervised
treatment schedules to ensure compliance, and sexual partners should be
rescreened. These patients could also be referred to the relevant experts
(pg 39).
Grade D, Level 4
D All pregnant women should be screened for syphilis at the initial
antenatal visit. Women who had documented treatment for syphilis in the
past do not need retreatment during current or subsequent pregnancies if
there is no clinical evidence of syphilis and the RPR/VDRL titre is
negative or serofast in low titre compared to previous results (pg 39).
Grade D, Level 4
7
D For penicillin-allergic patients, erythromycin is given in dosage
schedules as recommended for the treatment of non-pregnant patients.
However, as erythromycin exhibits poor penetration across the placental
barrier, the infant should be routinely treated with penicillin at birth. For
these patients, retreatment with doxycycline can be considered after
delivery when breastfeeding has been stopped (pg 40).
Grade D, Level 4
C Women treated for early syphilis during pregnancy should have
monthly rapid plasma regain (RPR) or Venereal Disease Research
Laboratory (VDRL) for the remainder of the current pregnancy (pg 40).
Grade C, Level 2+
Management of chancroid
D Locally, chancroid is uncommon. Any suspected case should be
referred to a specialist for evaluation, as routine laboratory tests are not
widely available (pg 40).
Grade D, Level 4
Treatment of chancroid (pg 40-41)
1. A Azithromycin 1 g orally x single dose.
OR
2. B Ceftriaxone 250 mg i/m x single dose.
OR
B Ciprofloxacin 500 mg bid x 3 days.
3. B
Grade A, Level 1+
Grade B, Level 2++
Grade B, Level 2++
Management of lymphogranuloma venereum
D Locally, lymphogranuloma venereum (LGV) is uncommon. Any
suspected case should be referred to a specialist for evaluation, as routine
laboratory tests are not widely available (pg 41).
Grade D, Level 4
8
Treatment of lymphogranuloma venereum (pg 41)
1. C Doxycycline 100 mg bid x 21 days.
OR
2. C Erythromycin 500 mg qid x 21 days.
Grade C, Level 2+
Grade C, Level 2+
Management of genital discharges
B Patients presenting with genital discharges should also be screened for
HIV and syphilis (pg 42).
Grade B, Level 2++
GPP The following diagnostic approach is recommended (pg 42-43):
A. Patient history:
1. History of discharge: onset, duration, colour, odour, association
with micturition, dysuria, itch, rash, chronicity, involvement of
sites (urethra, vagina, pharynx, rectum, eye), other systemic
symptoms (fever, joint pain, ophthalmic symptoms), use of
systemic or topical remedies, any history of similar symptoms in
the past or partners with similar symptoms.
2. Medical history: diabetes, HIV status, skin conditions, drug
allergies, current & previous medications, menstrual history,
obstetric history
symptoms or signs, partners with known genital discharge
diagnosis.
taken place.
B. Physical examination:
1. Lesion: appearance and character of discharge, consistency,
odour.
2. Genital exam: external genitalia and peri-anal area for
inflammation and other lesions.
size, tenderness.
4. General exam: thorough examination of oral cavity and
eyes/joints as necessary. In males, examine the penis carefully,
retract the foreskin if present, inspect the meatus for
9
inflammation, and look for urethral discharge. If there is no
discharge visible, gently ‘milk’ the urethra towards the meatus.
GPP
Genital discharges in males
D All patients who have confirmed or suspected urethritis should be tested
for gonorrhoea and chlamydia (pg 45).
Grade D, Level 4
B Because of high specificity (>99%) and sensitivity (>95%), a Gram
stain of a male urethral specimen that demonstrates polymorphonuclear
leukocytes with intracellular Gram-negative diplococci is presumptive of
infection with N.gonorrhoeae in symptomatic men. Thus it is
recommended that urethral smears be obtained in symptomatic men to aid
in diagnosis (pg 46).
Grade B, Level 2++
Chlamydia and gonorrhoea in women
B Microscopical examination of Gram-stained smears of endocervical
discharge can be used as a point of care test to provide an immediate
presumptive diagnosis of gonorrhoea (pg 46).
Grade B, Level 2++
B Gonococcal complement fixation test are not recommended for the
diagnosis of gonorrhea. Serological tests are not recommended for the
diagnosis of acute chlamydial infections (pg 47).
Grade B, Level 2++
10
10
Complications of genital discharges
D Syndromic management of urethral symptoms in males (pg 48)
Urethral symptoms present
Presence of sexually transmitted urethral infection
This is indicated if any one of the following are present:
History - risk of sexually transmitted infection present (e.g.
unprotected oral, vaginal, anal sex)
Examination - presence of urethral discharge and meatitis
Laboratory - raised polymorphonuclear leucocytes (PML) on Gramstained smear
Diagnosis of gonorrhoea is likely if there is Thick purulent discharge
Short incubation period (2-7 days)
Gram-negative intracellular diplococci seen on Gram-stain
microscopy
If any one of the above points are present Send urethral swab for gonococcal culture
Send urethral swab or first catch urine for nucleic-acid amplification
test (NAAT) for Chlamydia trachomatis
Treat for Neisseria gonorrhoeae and Chlamydia trachomatis
Review in 14 days
If none of the above points are present Send urethral swab for gonococcal culture
Send urethral swab or first catch urine for NAAT for Chlamydia
trachomatis
Treat for Chlamydia trachomatis
Review in 14 days
Grade D, Level 4
Treatment of gonorrhoea
x
Uncomplicated infection in adults - urethral, endocervical &
rectal infection (pg 49)
1.
A Ceftriaxone 250 mg intramuscular single dose.
OR
2.
A Cefixime 400 mg orally single dose.
11
11
Grade A, Level 1+
Grade A, Level 1+
Alternative regimens (pg 49)
1.
A Cefotaxime 1 g intramuscular single dose.
OR
2.
Grade A, Level 1+
A Spectinomycin 2 g intramuscular single dose (for patients with
E-lactam allergy).
Grade A, Level 1+
B All patients with gonorrhoea should be given concurrent treatment
for Chlamydia (pg 49).
Grade B, Level 2++
x Pharyngeal infection (pg 49)
B Ceftriaxone 250 mg intramuscular single dose with anti-chlamydia
therapy (refer to section 3.7).
Grade B, Level 2++
B The fluoroquinolones (e.g. ciprofloxacin, ofloxacin, norfloxacin)
should NOT be used as >70% of isolates in Singapore are resistant.
Grade B, Level 2++
x Gonococcal infection in pregnancy (pg 49-50)
A Cephalosporins in the recommended dosages are safe and effective
in pregnancy.
Grade A, Level 1+
A Spectinomycin can be administered to pregnant women who are
unable to tolerate cephalosporins.
Grade A, Level 1+
B Simultaneous treatment for chlamydial infection with azithromycin
1g single dose orally or erythromycin 500 mg orally qid x 7 to 14 days
is advocated for pregnant women receiving treatment of gonorrhoea.
Grade B, Level 2++
D Follow-up (pg 50)
-
Patients should be instructed to abstain from sexual intercourse until 7
days after therapy is initiated. After this period sexual activity can be
12
12
-
resumed provided their symptoms have resolved and sex partners have
been screened and treated.
The test-of-cure is recommended for all sites and assessment for postgonococcal urethritis (PGU) should be performed after 14 days.
All treatments are less effective at eradicating pharyngeal infection
and test-of-cure is strongly recommended following treatment of
infection at this site.
Serologic tests for syphilis and HIV should also be performed at the
initial visit; if negative they should be repeated at 3 months after the
last risky exposure.
Education on STIs and safer sex advice should be regularly
reinforced.
Grade D, Level 4
Management of sex partners
B Sexual contacts in the preceding 60 days should be traced, screened and
treated on epidemiologic grounds. If the last sexual exposure was > 60
days, the patient’s most recent partner should be treated (pg 50).
Grade B, Level 2++
Treatment of Chlamydia trachomatis infection
x
Uncomplicated urethral, endocervical, pharyngeal or rectal
infections in adults (pg 50-51)
1.
A Doxycycline 100 mg orally bid x 7 days.
OR
2.
A Azithromycin 1 g orally single dose.
OR
3.
Grade A, Level 1++
A Erythromycin 500 mg orally qid x 7 days or 500 mg orally bid x
14 days.
OR
4.
Grade A, Level 1++
Grade A, Level 1+
B
A Ofloxacin 200 mg orally bid or 400 mg orally od x 7 days.
Grade B, Level 2++
13
13
x
Chlamydia trachomatis infection in pregnancy (pg 51)
1.
A Erythromycin 500 mg orally qid x 7 days or 250 mg orally qid x
14 days.
OR
2.
A Amoxicillin 500 mg orally tid x 7 days.
OR
3.
A Azithromycin 1 g orally single dose.
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
Follow up
D A test-of-cure is not necessary when treatment with doxycycline or
azithromycin has been completed, unless symptoms persist or re-infection
is suspected. Test-of-cure is however recommended after 4 weeks for
infections in pregnant women, or when erythromycin was used. Nonculture tests (e.g. NAAT) done within 4 weeks of completing treatment
may yield false positive tests due to persistence of chlamydial antigens
(pg 51).
Grade D, Level 4
D Sex partners of symptomatic male patients within the last 60 days (or
the most recent sex partner if the last contact was >60 days) should be
screened and treated for chlamydial infection (pg 52).
Grade D, Level 4
D Sex partners of asymptomatic male patients and of females within the
last 90 days (or the most recent sex partner if the last contact was >90
days) should be screened and treated for chlamydial infection (pg 52).
Grade D, Level 4
14
14
Treatment of non-gonococcal urethritis (NGU)
D Sex partners of men with non-gonococcal urethritis (NGU) within the
last 60 days should be screened and treated. These partners should also be
examined to exclude other associated STI (pg 52).
Grade D, Level 4
Management of recurrent or chronic NGU
-
D Obtain objective evidence of urethritis, e.g. presence of urethral
discharge or pus cells on urethral smear. If patient has no objective
evidence, consider reassurance only.
- Exclude drug adherence failure or re-infection from untreated partner
or a new partner.
- Consider referral to a specialist for further evaluation.
(pg 53)
Grade D, Level 4
Vaginal discharge
B In women of reproductive age complaining of vaginal discharge the
commonest cause is physiological, but infective and other causes should
be excluded (pg 53).
Grade B, Level 2++
B A spontaneous complaint of abnormal vaginal discharge is most
commonly due to a vaginal infection, and rarely, it may be the result of
mucopurulent STI-related cervicitis. The symptom of abnormal vaginal
discharge is highly indicative of vaginal infection, but poorly predictive
for cervical infection. To ensure a cost-effective approach, risk assessment
should therefore be done before investigations and treatment is provided
(pg 54).
Grade B, Level 2++
B Where resources permit, one should consider the use of laboratory tests
to screen women with vaginal discharge. Such screening could be applied
to all women with discharge as well as to those with a positive risk
assessment (pg 55).
Grade B, Level 2++
15
15
GPP Investigation of a woman with vaginal discharge is indicated if
(Table 2) (pg 55):
1. She is deemed to be at high risk of sexually transmitted infections
(STI).
2. She has symptoms suggestive of upper genital tract infection (e.g.
abdominal pain, dyspareunia or fever).
3. She has previous treatment which failed.
4. She is postnatal, post-miscarriage, or post-abortion.
5. She is within 3 weeks of insertion of intrauterine contraceptive device.
6. Requested by the patient.
GPP
Table 2
Investigations for vaginal discharges
Site
Vulval fissures
and erythema
Vagina
Cervix
Investigations
Microscopy for yeasts
Culture for yeasts
Herpes simplex virus (if multiple vesicles or ulcers
present)
Wet preparation to detect Trichomonas vaginalis
(posterior fornix)
Gram stain to detect clue cells and yeasts (lateral
walls)
Culture for Trichomonas vaginalis and yeasts
(lateral walls and posterior walls)
Amine ‘sniff’ test (if available)
Vaginal pH (if available)
Gram-stain for pus cells, Gram-negative
intracellular diplococci
Culture Neisseria gonorrhoeae
Nucleic-acid amplification test (NAAT) for
Chlamydia trachomatis
B Not all women with vaginal discharge require investigation. Empirical
treatment can be given after taking a clinical and sexual history if (pg 56):
1. The woman is at low risk of STI.
2. She has no symptoms to suggest upper genital tract infection.
3. She can return for follow-up if symptoms do not resolve.
Grade B, Level 2++
16
16
B A woman of reproductive age complaining of vaginal discharge should
be investigated if (pg 56):
(STI).
5. She is within 3 weeks of insertion of intrauterine contraceptive device.
6. Investigation is requested by the patient.
Grade B, Level 2++
B
B The major causes for vaginal discharge include candidiasis, bacterial
vaginosis, trichomoniasis, Chlamydia trachomatis and gonococcal
infection. Depending on the physician assessment of the patient’s risk
factors, syndromic management may be directed against one or all of these
common causes (pg 56).
Grade B, Level 2++
Treatment of bacterial vaginosis (pg 59)
Indications for treatment:
1. A All symptomatic women with bacterial vaginosis, pregnant or non
pregnant.
Grade A, Level 1+
2.
A Asymptomatic women with bacterial vaginosis before surgical
procedures.
Grade A, Level 1+
D Patients with bacterial vaginosis should avoid vaginal douching, use of
shower gels, antiseptic agents or shampoo in the bath (pg 59).
Grade D, Level 3
Recommended regimens for bacterial vaginosis (pg 60):
1.
A Clindamycin cream 2% (5 g) intravaginally daily x 3 days or
Clindamycin site-released (SR) cream 2% (5 g) intravaginally x single
application.
OR
2.
A Clindamycin 300 mg orally bid x 7 days.
17
17
Grade A, Level 1+
Grade A, Level 1+
OR
3.
A Metronidazole gel 0.75% (5 g) intravaginally daily x 5 days.
OR
4.
A Metronidazole pessary (500 mg) intravaginally bid x 7 days or daily
x 14 days.
OR
5.
A Metronidazole 400 mg orally bid x 7 days.
OR
6
Grade A, Level 1+
A Tinidazole 2 g orally single dose.
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
Note:
1. A Metronidazole 2 g orally single dose therapy is the least effective
for bacterial vaginosis and is no longer recommended.
Grade A, Level 1+
2. Intravaginal metronidazole gel and clindamycin cream have similar
efficacy.
3. Metronidazole is less active against lactobacilli than clindamycin.
However, clindamycin is more active than metronidazole against
most of the bacteria associated with bacterial vaginosis.
Clindamycin reduces vaginal Mobiluncus to a greater extent than
metronidazole.
4. Clindamycin vaginal creams and suppositories may be oil-based
and might weaken latex condoms.
A If bacterial vaginosis causes vaginal discharge in pregnancy, it should
be treated as for non-pregnant women (pg 61).
Grade A, Level 1+
Recommended regimens for pregnant women (pg 61)
1.
Clindamycin-sustained released (SR) cream 2% (5 g) intravaginally x
single application.
OR
18
18
Grade A, Level 1+
2.
OR
3.
A Metronidazole pessary (500 mg) intravaginally bid x 7 days or daily
x 14 days.
OR
4.
Grade A, Level 1+
Grade A, Level 1+
A Metronidazole 400 mg orally bid x 7 days. (Avoid in first
trimester*).
Grade A, Level 1+
Note:
1. *Metronidazole crosses the placental barrier. Although it has been
given to pregnant women without apparent complication or
teratogenicity, it is advisable to withold oral or vaginal
metronidazole during the first trimester of pregnancy.
2. In three trials, intravaginal clindamycin cream was administered at
16-32 weeks’ gestation, and an increase in adverse events (e.g., low
birth-weight and neonatal infections) was observed in newborns.
Therefore, intravaginal clindamycin cream should only be used
during the first half of pregnancy.
Suggested suppressive therapy for recurrent bacterial vaginosis
(pg 62):
1.
A Metronidazole gel 0.75% (5 g) twice weekly for 4-6 months.
OR
2.
Grade A, Level 1+
C Metronidazole 400 mg orally bid for 3 days at the start and end of
menstruation.
Grade C, Level 2+
Suggested maintenance regime for recurrent bacterial vaginosis:
B Acetic acid vaginal gel use at the time of menstruation and following
unprotected sexual intercourse to maintain acidic vaginal Ph (pg 62).
Grade B, Level 2+
Follow up
D Follow-up is not necessary if symptoms resolve. A test of cure is not
required (pg 62).
Grade D, Level 4
19
19
Treatment of candidiasis
D Avoid local irritants (e.g. perfumed vaginal douch), scented panty-liners
and tight fitting synthetic clothing (pg 63).
Grade D, Level 4
Treatment for uncomplicated acute vulvovaginal candidiasis
A Both vaginal or oral antifungals (azoles) can be used in the treatment of
uncomplicated acute vulvovaginal candidiasis (pg 63).
Grade A, Level 1+
Recommended regimens for uncomplicated acute vulvovaginal
candidiasis (pg 63-64):
1.
A Butoconazole1-sustained released (SR) cream site 2% (5 g)
intravaginally x single application.
OR
2.
Grade A, Level 1+
A Clotrimazole pessary 200 mg intravaginally daily x 3 days or 100
mg or 1% cream (5 g) intravaginally daily x 7 days or 500 mg x single
application.
OR
3.
A Fluconazole 150 mg orally single dose.
OR
4.
A Itraconazole 200 mg orally bid x 1 day.
OR
6.
Grade A, Level 1+
Grade A, Level 1+
A Miconazole pessary 200 mg intravaginally daily x 3 days or 100 mg
or 2% cream (5 g) intravaginally daily x 7 days.
OR
7.
Grade A, Level 1+
A Isoconazole pessary 600 mg intravaginally x single application.
OR
5.
Grade A, Level 1+
A Nystatin pessary 100,000 U daily x 14 days.
20
20
Grade A, Level 1+
Grade A, Level 1+
Note:
1. All topical and oral azole therapies give a clinical and mycological
cure rate of 80-90% in uncomplicated vulvovaginal candidiasis.
Nystatin preparations give 70-90% cure rate.
2. The treatment choice is the personal preference, availability and
affordability as well as familiarity of the clinician with the
treatment.
3. Topical azole creams and suppositories may be oil-based and might
weaken latex condoms.
4. Topical azole treatment may cause vulvo-vaginal irritation and this
should be considered if symptoms worsen.
Follow up
GPP Follow-up is not necessary if symptoms resolve. A test of cure is
not required (pg 64).
GPP
Treatment of recurrent vulvovaginal candidiasis
GPP Clinicians should be aware of psychosexual problems and
depression, which can occur in women with recurrent vaginal infections
(pg 65).
GPP
Recommended regimens for recurrent vulvovaginal candidiasis
(pg 65-66):
Induction regimens
1. A Fluconazole 150 mg orally every 72 hours x 3 doses.
OR
2.
Grade A, Level 1+
C Topical imidazole therapy x 7-14 days according to symptomatic
response.
Grade C, Level 2+
Maintenance regimens
1. B Clotrimazole pessary 500 mg intravaginally once a week or 200 mg
intravaginally twice a week.
OR
2.
B Fluconazole 150 mg orally once a week.
21
21
Grade B, Level 2++
Grade B, Level 2++
Note:
1. B Maintenance therapy should last 6 months. 90% of women should
remain disease-free during treatment.
Grade B, Level 2++
C For women who have relapses between doses, consider twice2. C
weekly 150 mg fluconazole or 50 mg fluconazole daily.
Grade C, Level 2+
D Monitor the liver function test when the woman is on regular oral azole
treatment (pg 66).
Grade D, Level 4
Candidiasis in pregnancy
B Symptomatic candidiasis in pregnancy should be treated with topical
azole therapy only. Longer courses (seven days) are recommended. Oral
azole therapy is contraindicated (pg 67).
Grade B, Level 2+
Non-albicans candidiasis
Treatment (pg 67)
C Nystatin pessaries or nonfluconazole azole drug (oral or topical) are the
first line treatment for non-albicans infection.
OR
Grade C, Level 2+
C Consider Amphotericin B vaginal suppositories 50 mg once a day for
14 days.
Grade C, Level 2+
Trichomoniasis
D Sexual contacts in the preceding 60 days should be traced, screened and
treated on epidemiologic grounds. If the last sexual exposure was >60
days, the patient’s most recent partner should be treated (pg 68).
Grade D, Level 4
22
22
D Patients should be advised to avoid sexual intercourse (including oral
sex) until they and their partner(s) have completed treatment and followup (pg 68).
Grade D, Level 4
D Screening for coexisting sexually transmitted infections should be
undertaken in both the patients and their partners (pg 68).
Grade D, Level 4
C Women should be informed that T. vaginalis is a STI and partner
management and treatment is recommended for all partners in the last 2
months (pg 68).
Grade C, Level 2+
Treatment of trichomoniasis
Recommended regimen for trichomoniasis (pg 69):
1.
A Metronidazole 2 g orally x single dose.
OR
2.
OR
3
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
Note:
1. D Metronidazole gel is not recommended because it is less
efficacious (< 50%).
Grade D, Level 4
2. The recommended metronidazole regimes have resulted in cure
rates of 90-95%.
Trichomoniasis in pregnancy
D Although the use of metronidazole in pregnancy has not been shown to
be teratogenic or mutagenic in all stages of pregnancy or breastfeeding,
caution should be advised for use in the first trimester. Metronidazole
pessaries may be used to provide symptomatic relief but have lower cure
rates than the oral regimes (pg 69).
Grade D, Level 4
23
23
D Treatment of Trichomonas vaginalis relieves symptoms of vaginal
discharge in pregnant women and might prevent respiratory or genital
infection of the newborn and further sexual transmission. Clinicians
should counsel patients regarding the potential risks and benefits of
treatment (pg 69).
Grade D, Level 4
A It is reasonable to delay therapy in asymptomatic pregnant women until
after 37 weeks’ gestation. In addition, these pregnant women should be
provided careful counseling regarding condom use and the continued risk
of sexual transmission (pg 70).
Grade A, Level 1+
Follow up
A Follow-up is unnecessary for asymptomatic patients. Patients with
persistent symptoms should be retreated with metronidazole 400 mg orally
bid for 7 days (pg 70).
Grade A, Level 1+
A If treatment failure occurs repeatedly, the patient can be treated with
high dose oral metronidazole 2 g daily for 3 days (pg 70).
Grade A, Level 1+
GPP Doctors should consider efficacy, adverse side effects, dosing
frequency, and cost to the patient when recommending treatments. For
compliance issues, single dose therapies are generally recommended
(pg 71).
GPP
B Male patients complaining of urethral discharge and/or dysuria should
be examined for discharge. The major pathogens causing urethral
discharge are Neisseria gonorrhoeae and Chlamydia trachomatis. In the
syndromic management of a patient with urethral discharge, treatment
should adequately cover these two organisms and has been found to be
cost-effective. Where reliable laboratory facilities are available, a
distinction may be made between the two organisms (pg 71).
Grade B, Level 2++
24
24
1
1
Introduction
Introduction
1.1
Background information
These clinical practice guidelines have been produced to familiarize
doctors with the key features of the common sexually transmitted
causes of genital ulcers and discharges, to identify “red flags” that
indicate a need to refer the patient to a specialist, and to provide an
overview to evidence-based management of the various causes. The
guidelines are not intended to be a comprehensive review of all
aspects of genital ulcerative disease or discharge, or sexually
transmitted diseases.
1.2
Development of guidelines
These guidelines have been produced by a team comprising
dermatologists, obstetricians/gynaecologists, infectious disease
physicians, urologists, pathologists with an interest in laboratory
diagnosis of sexually transmitted infections, as well as general
practitioners.
1.3
Objectives
The main objective of these guidelines is to promote evidence-based
management of the common sexually transmitted causes of genital
ulcers and discharges. These guidelines will assist all doctors who
manage patients presenting with genital ulcers and discharges, in
particular primary care physicians, as well as dermatologists,
obstetricians and gynaecologists and infectious disease physicians
1.4
Review of guidelines
Evidence-based clinical practice guidelines are only as current as the
evidence that supports them. Users must keep in mind that new
evidence could supercede recommendations in these guidelines. The
workgroup advises that these guidelines be scheduled for review 5
years after publication, or when new evidence appears that requires
updating of the recommendations.
25
25
22 Management
Managementof
ofgenital
genitalulcers
ulcers
2.1
Introduction
The incidence of genital ulcer disease is on the rise in Singapore. This
is shown by the increase in notifications of patients seen at the
Department of STI Control Clinic (DSC) as well as from physicians in
hospital and general practice.1
Genital ulcer disease is associated with an increased risk for HIV
infection.2 The physician must also be aware that two or more
infections can coexist in a patient presenting with genital ulcers, and a
thorough evaluation of the possible causes should be undertaken.
Counselling and contact tracing, as far as possible, should also be
done. These management guidelines will cover the common sexually
transmitted infections causing genital ulcer disease.
2.2
Definition
Genital ulcer disease is defined as an ulcerative, erosive, pustular or
vesicular genital lesion(s) with or without regional lymphadenopathy,
caused by either sexually transmitted infections (STIs) or non-STIrelated infections or conditions.
Aetiology of genital ulcer disease
A. STI-related
The two commonest STIs which cause genital ulcerative disease are:
1. Genital herpes (HSV-1 or HSV-2) which is the leading cause, and
2. Primary syphilis
Other diseases such as Chancroid, Granuloma inguinale and
Lymphogranuloma venereum (due to Chlamydia trachomatis
serotypes L1, 2 or 3) are uncommon in Singapore.
26
26
B. Non-STI related infections or conditions3
Bullous dermatoses
x Non-autoimmune
1. Contact dermatitis
2. Erythema
multiforme
(commonly HSVrelated)
x Auto-immune
3. Pemphigus
2.3
Non-bullous
dermatoses
x Nonspecific
vulvitis/balanitis
x Apthous ulcers
x Erosive lichen
planus
x Lichen sclerosus
x Behcet’s disease
x Pyoderma
gangrenosum
x Fixed drug eruption
Malignancy
x Squamous cell
carcinoma
x Vulval
intraepithelial
neoplasia
x Erythroplasia of
Queyrat
Less common:
x Extramammary
Paget’s disease
x Basal cell carcinoma
Clinical approach to genital ulcers
D It is recommended that the following diagnostic approach be taken
in any patient with genital ulcers or discharges:
A. Patient history4:
1. Lesion history: prodrome, initial presentation (especially
presence of vesicles), duration of lesion, pain, symptoms of
urethritis, other systemic symptoms, use of systemic or topical
remedies, any history of similar symptoms in the past or partners
with similar symptoms.
2. Medical history: HIV status, skin conditions, drug allergies, and
medications.
symptoms or signs, partners with known HSV or recent syphilis
diagnosis.
taken place.
B. Physical exam4:
1. Lesion: examine for appearance, distribution, number, size,
induration, depth, and tenderness.
2. Genital exam: examine genital and perianal area for other lesions.
size, tenderness, presence of bubo.
27
27
4.
General exam: thorough examination of oral cavity and skin of
torso, palms and soles. In patients with syphilis, this would
include an examination of the cardiovascular and neurological
systems.
Grade D, Level 4
Table 1
Aetiologic
agent
Incubation
period
Initial
lesions
Presenting
lesion
Number and
distribution
of lesions
Clinical features of some causes of genital
ulcers
Genital Herpes
Primary Syphilis Chancroid
T. pallidum
H. ducreyi
HSV-1 & HSV-2
- uncommon
- most common cause
locally
2-7 days
10-90 days
3-10 days
(avg. 21 days)
(avg. 4-7 days)
Papule Æ vesicle*
Papule
Papule or pustule
Vesicles
Chancre
Usually one
Multiple*, may
coalesce.
Bilateral in primary;
unilateral in recurrent.
Single or multiple
1-2 mm
Erythematous
Variable
Undermined,
ragged, irregular
5-15 mm
Sharply
demarcated,
elevated, round, or
oval
Superficial
Superficial or
Depth
deep
Serous, erythematous, Smooth, nonBase
nonvascular
purulent,
relatively
nonvascular
Usually present
Induration None
Common, often with Uncommon*
Pain
prodrome of tingling*
Firm, non-tender,
Lymphaden Usually present in
primary infection, and bilateral
opathy
absent in recurrences
Diameter
Edges
Ulcer/bubo
Excavated, deep
Necrotic,
generally
purulent, bleeds
easily
None
Common, severe
Tender, may
suppurate, usually
unilateral
Source: Holmes KK, Sparling PF, Mardh P-A, Lemon SM, Stamm WE, Plot P,
Wasserheit JN. Sexually Transmitted Diseases 3rd Edition; McGraw Hill. Chap
64 Pg 888 Table 64-2.
*Useful in differential diagnosis.
28
28
C. Laboratory testing
A A diagnosis based only on the patient’s medical history and
physical examination frequently may be inaccurate. Ideally, all
patients who have genital ulcers should be evaluated with a serologic
test for syphilis and a diagnostic evaluation for genital herpes; if
chancroid is suspected, the patient should be referred to a specialist
for evaluation and a test for Haemophilus ducreyi.5,6,7
Grade A, Level 1+
B HIV and serologic testing for syphilis should be performed on all
patients who have STIs presenting with genital ulcers8, as well as tests
for herpes simplex infection where appropriate. Locally, genital
herpes and syphilis are the two most likely infective etiologies. Noninfective causes may need to be considered.8,9
Grade B, Level 2++
D. Management
Clinicians often have to treat patients before test results are available
because early treatment decreases the possibility of ongoing
transmission and because successful treatment of genital herpes
depends on prompt initiation of therapy.
B The clinician should treat for the diagnosis considered most likely,
on the basis of clinical presentation and epidemiologic circumstances.
In some instances, treatment must be initiated for additional
conditions because of diagnostic uncertainty.5
Grade B, Level 2++
GPP Successful management of STI-associated syndromes requires
that staff are respectful of patients and are not judgmental.
Examination must be done in appropriate surroundings where privacy
can be ensured and confidentiality guaranteed. Patients should be
educated and counseled on their condition as well as safer sex.
GPP
Even after complete diagnostic evaluation, at least 25% of patients
who have genital ulcers have no laboratory-confirmed diagnosis.5
29
29
A syndromic approach to management of genital ulcers has proven to
be cost-effective in resource poor settings; however it has not been
shown to be applicable in the local context.8,9
2.4
Management of specific genital ulcer diseases
2.4.1
Management of herpes simplex virus (HSV) infection
2.4.1.1
Clinical features
Genital herpes is caused by HSV type 1 or 2. First episode genital
herpes is often severe, presenting with multiple grouped vesicles,
which rupture easily leaving painful erosions and ulcers. In the male,
the lesions occur mainly on the prepuce and sub-preputial areas of the
penis; in females on the vulva, vagina and cervix. Healing of
uncomplicated lesions takes 2 to 4 weeks.
Recurrent attacks are less severe than the first episode. Groups of
vesicles or erosions develop on a single anatomical site and these
usually heal within 10 days.
The majority of persons with HSV infection have mild, often
unrecognised or sub-clinical disease and are unaware of the infection.
They may nevertheless shed the virus intermittently in the genital tract
and thus transmit the infection to their partners unknowingly.
2.4.1.2
•
Laboratory investigations
Viral isolation in cell culture:
This is considered the ‘Gold standard’. The test is both sensitive
and specific, but sensitivity declines as lesions heal; viral typing
is possible.10-12
The swab used for sampling the cells at the bases of ulcers should
be sent in viral transport medium, which can be obtained from the
laboratories performing the test. Do not use calcium alginate
swabs, however cotton-, rayon-, or dacron-tipped swabs are
suitable. Insert the swab into the viral transport medium, break
off the stick and screw-cap the bottle securely. The sample then
needs to be dispatched to the laboratory at 4oC using an ice pack.
If delay is anticipated, refrigerate at 4oC, do not freeze. Time
30
30
taken for a positive result (HSV type 1 or 2) ranges from 1 to 7
days, and for a negative result 7 days.
OR
•
HSV antigen detection:
By Direct Immunoflouresence techniques.
The swab used for sampling the cells at the base of ulcers can be
sent in a sterile container with 1 to 2 mL of sterile saline added to
prevent drying of the swab. Refrigerate sample at 4oC until
transfer to the laboratory, do not freeze. Results may be available
in 1 to 2 days. HSV type is reported if the test is positive.
OR
•
PCR detection of viral nucleic acid:
Highest sensitivity; viral typing possible11,12; but expensive and
not widely available. Use only Dacron-tipped swabs and send
swab in swab sheath without any media. Refrigerate sample at
4oC until transfer to the laboratory, do not freeze. Dispatch to the
laboratory at 4oC using an ice pack. Results are available in 2 to
4 days.
What about serology?
The role of Type-specific serological tests (TSST):
Many commercial tests for HSV antibodies are not type specific and
are of NO value in the management of genital herpes.13-16
Accurate type-specific assays for HSV antibodies must be based on
the HSV-specific glycoprotein G1 for the diagnosis of infection with
HSV-1 and glycoprotein G2 for the diagnosis of HSV-2.
B In performing serology for HSV infection, assays that detect the
type-specific glycoproteins gG1 (HSV 1) and gG2 (HSV 2) should be
used.
Grade B, Level 2++
The presence of specific IgG to HSV indicates previous exposure.
31
31
The use of TSST may be useful in certain specific situations, such as
confirming a diagnosis of genital herpes in a person with a typical
history of recurrent ulcers but negative cultures, counselling of sexual
partners of infected persons, detection of unrecognized infection and
for seroepidemiological studies.16
Because almost all HSV-2 infections are sexually acquired, typespecific HSV-2 antibody indicates anogenital infection, but the
presence of HSV-1 antibody does not distinguish anogenital from
orolabial infection.
2.4.1.3
Treatment
Treatment of first episode genital herpes
1.
A Acyclovir 200 mg orally 5 times daily for 5 to10 days.17
OR
2.
A Acyclovir 400 mg orally tid for 5 to10 days.17
OR
3.
Grade A, Level 1++
A Valacyclovir 500 mg/1g orally bid for 5 to 10 days.18
OR
4.
Grade A, Level 1++
B Famciclovir 250 mg orally tid for 5 to 10 days.5
Grade A, Level 1++
Grade B, Level 2++
Recurrent genital herpes
Most recurrent attacks are mild and can be managed with general
measures/supportive therapy.
Management should be decided together with the patient and can be
divided into episodic or suppressive treatment.
Episodic treatment – Effective episodic treatment of recurrent herpes
requires initiation of therapy during the prodrome or within 1 day of
lesion onset.
C For episodic treatment of recurrent herpes, the patient should be
provided with a supply of drug or a prescription for the medication
32
32
with instructions to self-initiate treatment immediately when
symptoms begin.13
Grade C, Level 2+
Treatment of recurrent genital herpes
1.
A Acyclovir 200 mg orally 5 times daily or 400 mg orally tid or
800 mg orally bid for 5 days.19
OR
2.
A Acyclovir 800 mg tid orally for 2 days.20
OR
3.
for 5 days.21
A Valacyclovir 500 mg bid for 3 days.22,23
OR
5.
A Famciclovir 125 mg orally bid for 5 days.24
OR
6.
Grade A, Level 1++
A Valacyclovir 500 mg orally bid or 1000 mg orally once a day
OR
4.
Grade A, Level 1++
A Famciclovir 1 g bid orally for 1 day.25
Grade A, Level 1++
Grade A, Level 1++
Grade A, Level 1++
Grade A, Level 1++
Suppressive treatment
C Suppressive therapy reduces the frequency of genital herpes
recurrences and may be considered in patients who have frequent
recurrences (i.e. 6 or more recurrences per year).13
Grade C, Level 2+
Suppressive treatment of recurrent genital herpes
1.
A Acyclovir 400 mg orally bid.26,27
OR
2.
A Valacyclovir 500 mg orally od.28
33
33
Grade A, Level 1+
Grade A, Level 1+
OR
3.
A Valacyclovir 1000 mg orally od (for > 10 recurrences in 1
year).5,29
OR
4.
A Famciclovir 250 mg orally bid.30
Grade A, Level 1+
Grade A, Level 1+
C Physicians should stop suppressive treatment of genital herpes after
9 to 12 months to see if recurrence occurs and continued prophylaxis
is warranted.13
Grade C, Level 2+
Treatment of genital herpes in HIV-infected patients31
1.
A Acyclovir 400 mg orally tid for 7 to 10 days.32
OR
2.
A Valacyclovir 1 g orally bid for 7 to 10 days.32
OR
3.
Grade A, Level 1+
Grade A, Level 1+
A Famciclovir 500 mg orally bid for 7 to 10 days.33
Grade A, Level 1+
Suppressive treatment of genital herpes in HIV-infected patients
1.
A Acyclovir 400 mg to 800 mg orally bid or tid.34
OR
2.
A Valacyclovir 500 mg orally bid.32,35
OR
3.
A Famciclovir 500 mg orally bid.36
34
34
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
2.4.1.4
Management of genital herpes in pregnancy
Neonatal herpes is a rare but serious condition, caused by herpes
simplex virus type 1 or herpes simplex virus type 2. Neonatal herpes
is almost always acquired by direct contact with infected maternal
secretions at birth.37,38
The most severe form of the disease is disseminated infection with
multiple organ involvement, where mortality is around 30% and 17%
have long-term neurologic sequelae.37
The risk of transmission to a neonate is high (30-50%) in women who
acquire genital herpes late in pregnancy and low (<1%) in women
with recurrent genital herpes at term or who acquire genital herpes
during the first half of pregnancy.38
Although acyclovir is not licensed for use in pregnancy, there is
substantial clinical experience supporting its safety.39
First episode genital herpes – 1st and 2nd trimester acquisition
C Management should be in line with the clinical condition with the
use of either oral or intravenous acyclovir.40
Grade C, Level 2+
C Vaginal delivery is anticipated in women who present with first
episode genital herpes in the first and second trimesters as the risk for
transmission to the neonate at delivery is low.40
Grade C, Level 2+
First episode genital herpes – 3rd trimester acquisition
C Caesarean section should be offered to all women presenting with
first-episode genital herpes lesions at the time of delivery, or within 6
weeks of the expected date of delivery or onset of labour.41-43
Grade C, Level 2+
35
35
Recurrent genital herpes in pregnancy
C If there are no genital lesions at the onset of labour, Caesarean
section to prevent neonatal herpes is not indicated.40-43
Grade C, Level 2+
A For women with a history of recurrent genital herpes, who would
opt for caesarean delivery if HSV lesions were detected at the onset of
labour, daily suppressive acyclovir given from 36 weeks of gestation
until delivery may be given to reduce the likelihood of HSV lesions at
term).44-47
Grade A, Level 1+
B Counselling for genital herpes is important and should
include48:
• Information on natural history of disease, potential for recurrent
attacks, role of asymptomatic shedding in sexual transmission
• Abstinence from sexual activity during prodromal symptoms or
when lesions are present
• Advice to inform current and new sexual partners of genital
herpes
• Use of condoms with new or uninfected partners, particularly in
first 12 months after first attack
• Information on anti-viral treatment available
• Risk of neonatal infection: women with a history of genital herpes
or whose partners have history of genital herpes should inform
their obstetrician early in pregnancy
Grade B, Level 2++
2.3.2
Management of primary syphilis
2.3.2.1
Clinical features
Primary syphilis is characterised by an ulcer (chancre) and regional
lymphadenopathy. A chancre typically occurs in the anogenital
region, and presents as a solitary, painless and indurated ulcer with a
clean base discharging clear serum.49 However, atypical features may
be present; these include multiple lesions, presence of pain, and
occurrence on extragenital sites.50
36
36
2.3.2.2
Laboratory investigations
Serological Tests
I
Non-Treponemal Tests – rapid plasma regain (RPR) and/or
Venereal Disease Research Laboratory (VDRL)
A positive RPR/VDRL test needs to be confirmed by a
treponemal test. RPR/VDRL may become negative if treatment is
instituted early in the disease. However treatment of late
infections often results in a persistently positive result - or a
serological scar.
II
Treponemal Tests (confirmatory)
x The Treponema Pallidum Haemagglutination Assay
(TPHA) and the Treponema Pallidum Particle
Agglutination (TPPA) test are the most widely used
confirmatory tests.
x The treponemal EIA test is also a specific test for syphilis,
but most experts recommend performing either TPHA or
TPPA as an additional confirmatory test if the EIA result is
positive.
x Once positive, specific tests tend to remain positive even
after the syphilis has been successfully treated. The titres of
treponemal tests are not useful in monitoring treatment
response.
2.3.2.3
Treatment
Treatment of primary syphilis
1.
B Benzathine Penicillin G 2.4 million units i/m weekly x single
dose. (For primary syphilis, most authorities administer a single
dose, while some might use two doses for secondary syphilis).51,52
OR
2.
Grade B, Level 2++
B Aq. Procaine Penicillin G 600,000 units i/m daily x 10 days.53-55
Grade B, Level 2++
37
37
Penicillin-allergic patients
1.
Doxycycline 100 mg orally bid x 14 days.56-58
OR
2.
Erythromycin 500 mg orally qid x 14 days.59,60
OR
3.
Azithromycin 500 mg orally od x 10 days.61
Grade B, Level 2++
Grade B, Level 2++
Grade B, Level 1+
C For HIV-infected individuals, either the same treatment as in non-
HIV infected individuals or 3 doses of Benzathine Penicillin G 2.4
million units i/m weekly are recommended.9 [0]
Grade C, Level 2+
C HIV-positive individuals with primary syphilis should be referred
to an appropriate expert for follow up.9
Grade C, Level 2+
B Oral doxycycline is the preferred oral alternative in all patients in
view of its more favourable dosing intervals and low cost.58
Grade B, Level 2++
GPP The treatment guidelines listed refer to management of primary
syphilis. For late latent syphilis, syphilis of unknown duration,
congenital syphilis or neurosyphilis, the treatment recommendations
are different and relevant expert advice should be sought.
GPP
2.3.2.4
Follow-up
C The same quantitative nontreponemal tests (i.e RPR or VDRL)
should be repeated during follow up; the DSC Clinic follows up
patients for a total period of two years (tests are repeated at 3 months;
6 months; 12 months; 18 months; 24 months).9,53
Grade C, Level 2+
C A sustained fourfold or greater increase in RPR/VDRL titres
suggests re-infection or treatment failure. Following treatment of early
syphilis, RPR/VDRL should demonstrate a decrease in titre within 6
38
38
months. In particular, patients treated with non-penicillin based
regimens should be followed up to look for signs of treatment
failure.9,53
Grade C, Level 2+
C Since treponemal tests remain positive for life following effective
treatment, proper documentation is necessary to prevent unnecessary
retreatment. Patients should be given a letter documenting their
treatment.9
Grade C, Level 2+
D Reinfection or relapse should be retreated preferably with
supervised treatment schedules to ensure compliance, and sexual
partners should be rescreened. These patients could also be referred to
the relevant experts.9
Grade D, Level 4
2.3.2.5
Management of sexual contacts
Partner notification, or “contact tracing”, is the process of learning
from persons with STIs about their sexual partners and helping to
arrange for evaluation and treatment of those partners. Many persons
benefit from partner notification; thus patients with STIs should be
encouraged to make partners aware of potential risk and urge them to
seek diagnosis and treatment.
At risk partners are those who have been exposed within the following
periods – 3 months plus duration of symptoms for primary syphilis.
There is clear evidence that involving index patients in shared
responsibility for the management of sexual partners improves
outcomes.62
Syphilis in pregnancy
Penicillin is the drug of choice in the same dosage schedule as for
non-pregnant individuals.
D All pregnant women should be screened for syphilis at the initial
antenatal visit. Women who had documented treatment for syphilis in
the past do not need retreatment during current or subsequent
pregnancies if there is no clinical evidence of syphilis and the
39
39
RPR/VDRL titre is negative or serofast in low titre compared to
previous results.9
Grade D, Level 4
D For penicillin-allergic patients, erythromycin is given in dosage
schedules as recommended for the treatment of non-pregnant patients.
However, as erythromycin exhibits poor penetration across the
placental barrier, the infant should be routinely treated with penicillin
at birth. For these patients, retreatment with doxycycline can be
considered after delivery when breastfeeding has been stopped.9
Grade D, Level 4
Doxycycline is contraindicated in pregnancy.
C Women treated for early syphilis during pregnancy should have
monthly RPR/VDRL for the remainder of the current pregnancy.9
Grade C, Level 2+
2.4.3
Management of chancroid
2.4.3.1
Clinical features
Chancroid is caused by Haemophilus ducreyi. It is characterised by
genital ulceration and lymphadenitis with progression to bubo
formation. The incubation period ranges from 3 to 10 days. There may
be single or multiple ulcers, which are not indurated, bordered by
ragged undermined edges and have a necrotic base and purulent
exudate, and are typically painful.63
D Locally, chancroid is uncommon. Any suspected case should be
referred to a specialist for evaluation, as routine laboratory tests are
not widely available.1
Grade D, Level 4
2.4.3.2
1.
Treatment of chancroid
A Azithromycin 1 g orally x single dose.64
OR
40
40
Grade A, Level 1+
2.
B Ceftriaxone 250 mg i/m x single dose.65
OR
3.
2.4.4
B Ciprofloxacin 500 mg bid x 3 days.66
Grade B, Level 2++
Grade B, Level 2++
Management of lymphogranuloma venereum
2.4.4.1
Clinical features
Lymphogranuloma venereum (LGV) is a systemic disease caused by
one of three invasive serovars L1, L2 or L3 of Chlamydia
trachomatis.
Rectal exposure in women or men who have sex with men might
result in proctocolitis (including mucoid and/or hemorrhagic rectal
discharge, anal pain, constipation, fever, and/or tenesmus). LGV is an
invasive, systemic infection, and if it is not treated early, LGV
proctocolitis might lead to chronic, colorectal fistulas and strictures.60
There have been recent outbreaks described among men who have sex
with men in Western Europe and the United States.67,68
D Locally, lymphogranuloma venereum (LGV) is uncommon. Any
suspected case should be referred to a specialist for evaluation, as
routine laboratory tests are not widely available.1
Grade D, Level 4
2.4.4.2
1.
Treatment of lymphogranuloma venereum
B
C Doxycycline 100 mg bid x 21 days.69
OR
2.
C Erythromycin 500 mg qid x 21 days.69
B
41
41
Grade C, Level 2+
Grade C, Level 2+
33 Management
Management of
of genital
genital discharges
discharges
3.1
Introduction
In patients presenting with a urethral discharge, gonorrhoea and
Chlamydia trachomatis infections are the most common causes in
Singapore.70 A spontaneous complaint of abnormal vaginal discharge
is most commonly due to a vaginal infection, and less commonly may
be the result of mucopurulent STI-related cervicitis.
Genital discharges are associated with an increased risk for acquiring
HIV infection.71 Two or more infections may coexist in a patient
presenting with a genital discharge, therefore a thorough evaluation of
the possible causes should be undertaken. As far as possible,
counselling and contact tracing should be done. There may be a need
to treat the contact epidemiologically. These management guidelines
will cover the common infections causing genital discharges.
B Patients presenting with genital discharges should also be screened
for HIV and syphilis.8,9
3.2
Grade B, Level 2++
Diagnostic approach
GPP The following diagnostic approach is recommended:
A. Patient history:
1. History of discharge: onset, duration, colour, odour, association
with micturition, dysuria, itch, rash, chronicity, involvement of
sites (urethra, vagina, pharynx, rectum, eye), other systemic
symptoms (fever, joint pain, ophthalmic symptoms), use of
systemic or topical remedies, any history of similar symptoms in
the past or partners with similar symptoms.
2. Medical history: diabetes, HIV status, skin conditions, drug
allergies, current & previous medications, menstrual history,
obstetric history
symptoms or signs, partners with known genital discharge
diagnosis.
taken place.
42
42
B. Physical examination:
1. Lesion: appearance and character of discharge, consistency,
odour.
2. Genital exam: external genitalia and peri-anal area for
inflammation and other lesions.
size, tenderness.
4. General exam: thorough examination of oral cavity and
eyes/joints as necessary. In males, examine the penis carefully,
retract the foreskin if present, inspect the meatus for
inflammation, and look for urethral discharge. If there is no
discharge visible, gently ‘milk’ the urethra towards the meatus.
GPP
3.3
Genital discharges in males
Urethritis is a common cause of genital discharges in males.
Clinical features
Symptoms of urethritis include discharge, dysuria, and intra-urethral
itch/discomfort. The quantity of discharge ranges from minimal to
profuse, and it may be continuous or intermittent. The colour and
consistency of the discharge ranges from clear, mucoid, white,
mucopurulent, to frankly purulent. The presence of a urethral
discharge is almost always indicative of urethral infection. Dysuria in
sexually active young to middle-aged men often indicates a urethral
infection, whereas in older men a urinary tract infection is a more
likely diagnosis. Nevertheless urethral infections due to sexuallytransmitted pathogens may be asymptomatic.
43
43
Causes of sexually transmitted urethritis in males
Common causes
Neisseria gonorrhoeae
Other causes
Ureaplasma urealyticum
Mycoplasma genitalium
Trichomonas vaginalis
Herpes simplex virus
Adenovirus infection
Neisseria meningitidis
Non-specific urethritis (NSU)
Gonococcal urethritis has a shorter incubation period (2-7 days) than
NGU and is characterised clinically by a profuse purulent discharge
from the affected genital site (>80% in male urethritis, up to 50% in
female cervicitis), often accompanied by local pain or discomfort.
However asymptomatic infection occurs in 10% of urethral infection,
>50% of cervical infection, >90% of pharyngeal and rectal infection.
Non-gonococcal urethritis (NGU) refers to any urethritis from which
N. gonorrhoeae cannot be detected or isolated. NGU often has milder
symptoms, with scant discharge, and a longer incubation period (7-21
days). Urethritis which is not caused by N.gonorrhoeae may be due
to Chlamydia trachomatis (up to 50%) and other organisms (10% to
20%) including Ureaplasma urealyticum, Mycoplasma genitalium,
Trichomonas vaginalis, bacterial urinary tract infection and Herpes
simplex virus. The remainder (20-30%) have no detectable organisms
(non-specific urethritis).
44
44
Approach to diagnosis of urethral discharges
Diagnosis
Clinical feature
Nature of discharge
Clinical
complications
Urethral smear
Gram stain
Polymorph
Gram negative
intracellular
diplococci
Culture/nucleicacid amplification
test (NAAT)
Gonorrhoea
Purulent
Profuse
Epididymo-orchitis
Prostatitis
Non-gonococcal
urethritis
Clear, whitish
Epididymo-orchitis
Prostatitis
Disseminated
gonococcal infection
(DGI)
Reiter’s Disease
+/++
+/++ (> 5 wbcs/hpf)
+
-
N.gonorrhoeae
C.trachomatis
U.urealyticum
M.genitalium
M.hominis
Investigations in males:
Small amounts of discharge may have been washed away if the patient
has recently voided. In such cases the patient should be asked to return
4 hours after holding his urine when the laboratory tests can be
performed.
D All patients who have confirmed or suspected urethritis should be
tested for gonorrhoea and chlamydia.9
Grade D, Level 4
Testing for chlamydia is strongly recommended because of the
increased utility and availability of highly sensitive and specific
testing methods and because a specific diagnosis might enhance
partner notification/management and improve compliance with
treatment, especially in the exposed partner.72
45
45
B Because of high specificity (>99%) and sensitivity (>95%), a Gram
stain of a male urethral specimen that demonstrates
polymorphonuclear leukocytes with intracellular Gram-negative
diplococci is presumptive of infection with N.gonorrhoeae in
symptomatic men. Thus it is recommended that urethral smears be
obtained in symptomatic men to aid in diagnosis72,73
Grade B, Level 2++
Microscopy is not suitable for pharyngeal or rectal specimens where
many other bacteria are present including Gram-negative cocci
belonging to other genera.73
Cultures and PCR detection for Ureaplasma urealyticum and
Mycoplasma genitalium are not routinely performed.
Acute NGU is diagnosed when there are 5 or more polymorphic
leucocytes (PML) present per high-power field in 5 or more fields
using high power (1000x) oil- immersion microscopic examination of
a properly prepared urethral smear.
3.4
Chlamydia and gonorrhoea in women
C.trachomatis is a common bacterial STI in women. It is usually
asymptomatic (in 80% of women). However, women may present
with vaginal discharge (due to cervicitis), abnormal bleeding
(postcoital or intermenstrual), lower abdominal pain, dyspareunia or
dysuria. Risk factors for C.trachomatis are: age <25 years, a new
sexual partner or more than one partner in the last year.74-76
N.gonorrhoeae is another common bacterial STI in women. Up to
50% of women with N.gonorrhoeae will complain of vaginal
discharge. The discharge is due to cervicitis rather than vaginitis.
N.gonorrhoeae may coexist with other genital tract pathogens such as
Trichomonas, Candida and C.trachomatis.77
B Microscopical examination of Gram-stained smears of endocervical
B
discharge can be used as a point of care test to provide an immediate
presumptive diagnosis of gonorrhoea.73
Grade B, Level 2++
46
46
Microscopy of endocervical smears in women has a sensitivity of
between 30-50%.73
Blood tests such as the gonococcal complement fixation test (GCCFT) are not useful for the diagnosis of gonorrhoea. Serological tests
are also not useful in the diagnosis of acute chlamydial infections
because of cross-reactivity between chlamydial species, and the high
prevalence of Chlamydia antibodies in high risk populations.73
B Gonococcal complement fixation test are not recommended for the
diagnosis of gonorrhea. Serological tests are not recommended for the
diagnosis of acute chlamydial infections.
Grade B, Level 2++
3.5
Complications of genital discharges
Epididymo-orchitis due to retrograde spread of urethral infection is a
relatively uncommon but well-known complication of untreated
urethritis. N.gonorrhoeae and C.trachomatis are the commonest
causes.
Reactive arthritis or Reiter’s syndrome (the classic triad of arthritis,
conjunctivitis, and urethritis, sometimes with circinate balanitis and
keratoderma blenorrhagica) is most frequently triggered by Chlamydia
trachomatis urethritis.
Pelvic inflammatory disease (PID) may occur in untreated females.
As PID can cause serious sequelae such as infertility & ectopic
pregnancy as a result of tubal damage, investigation AND treatment is
warranted. Chronic pelvic pain may also occur.
Syndromic management can be applied to urethritis in males in view
of the relatively short list of pathogens, fairly specific clinical features
and small number of differential diagnoses.
47
47
D Syndromic management of urethral symptoms in males
Urethral symptoms present
Presence of sexually transmitted urethral infection
This is indicated if any one of the following are present:
History - risk of sexually transmitted infection present (e.g.
unprotected oral, vaginal, anal sex)
Examination - presence of urethral discharge and meatitis
Laboratory - raised polymorphonuclear leucocytes (PML) on
Gram-stained smear
Diagnosis of gonorrhoea is likely if there is Thick purulent discharge
Short incubation period (2-7 days)
Gram-negative intracellular diplococci seen on Gram-stain
microscopy
If any one of the above points are present Send urethral swab for gonococcal culture
Send urethral swab or first catch urine for nucleic-acid
amplification test (NAAT) for Chlamydia trachomatis
Treat for Neisseria gonorrhoeae and Chlamydia trachomatis
Review in 14 days
If none of the above points are present Send urethral swab for gonococcal culture
Send urethral swab or first catch urine for NAAT for
Treat for Chlamydia trachomatis
Review in 14 days
Grade D, Level 4
Source: World Health Organisation. Sexually Transmitted and Other
Reproductive Tract Infections Integrating STI/RTI Care for Reproductive
Health. A guide to essential practice. WHO 2005:116-7.
48
48
3.6
Treatment of gonorrhoea
x
Uncomplicated infection in adults - urethral, endocervical &
rectal infection
1.
A Ceftriaxone 250 mg intramuscular single dose.78-80
OR
2.
A Cefixime 400 mg orally single dose.78-80
Grade A, Level 1+
Grade A, Level 1+
Alternative regimens
1. A Cefotaxime 1 g intramuscular single dose.72,78,79,81
OR
2.
Grade A, Level 1+
A Spectinomycin 2 g intramuscular single dose (for patients
with E-lactam allergy).72,78,79,81
Grade A, Level 1+
B All patients with gonorrhoea should be given concurrent
treatment for Chlamydia.82
x
Grade B, Level 2++
Pharyngeal infection
B Ceftriaxone 250 mg intramuscular single dose79,83 with anti-
chlamydia therapy (refer to section 3.7).
Grade B, Level 2++
B The fluoroquinolones (e.g. ciprofloxacin, ofloxacin,
norfloxacin) should NOT be used as >70% of isolates in
Singapore are resistant.70
Grade B, Level 2++
x
Gonococcal infection in pregnancy
A Cephalosporins in the recommended dosages are safe and
effective in pregnancy.84-86
Grade A, Level 1+
49
49
A Spectinomycin can be administered to pregnant women who
are unable to tolerate cephalosporins.84-86
Grade A, Level 1+
B Simultaneous treatment for chlamydial infection with
azithromycin 1g single dose orally or erythromycin 500 mg orally
qid x 7 to 14 days is advocated for pregnant women receiving
treatment of gonorrhoea.84-86
Grade B, Level 2++
D Follow-up9
-
-
Patients should be instructed to abstain from sexual intercourse
until 7 days after therapy is initiated. After this period sexual
activity can be resumed provided their symptoms have resolved
and sex partners have been screened and treated.
The test-of-cure is recommended for all sites and assessment for
post-gonococcal urethritis (PGU) should be performed after 14
days.
All treatments are less effective at eradicating pharyngeal
infection and test-of-cure is strongly recommended following
treatment of infection at this site.
Serologic tests for syphilis and HIV should also be performed at
the initial visit; if negative they should be repeated at 3 months
after the last risky exposure.
Education on STIs and safer sex advice should be regularly
reinforced.
Grade D, Level 4
B Sexual contacts in the preceding 60 days should be traced, screened
and treated on epidemiologic grounds. If the last sexual exposure was
> 60 days, the patient’s most recent partner should be treated.9
Grade B, Level 2++
3.7
Treatment of Chlamydia trachomatis infection
x
Uncomplicated urethral, endocervical, pharyngeal or rectal
infections in adults
1. A Doxycycline 100 mg orally bid x 7 days.71,72
OR
50
50
Grade A, Level 1++
2.
A Azithromycin 1 g orally single dose.71,72
OR
3.
Grade A, Level 1++
A Erythromycin 500 mg orally qid x 7 days or 500 mg orally
bid x 14 days.71,72
Grade A, Level 1+
OR
4.
B Ofloxacin 200 mg orally bid or 400 mg orally od x 7
A
days.71,72
Grade B, Level 2++
x
Chlamydia trachomatis infection in pregnancy
Pregnant women whose sexual partners have non-gonococcal
urethritis (NGU) should be examined, screened for other STI, and
treated on epidemiological grounds.
1.
A Erythromycin 500 mg orally qid x 7 days or 250 mg orally
qid x 14 days.87-89
OR
2.
A Amoxicillin 500 mg orally tid x 7 days. 87-89
OR
3.
A Azithromycin 1 g orally single dose. 87-89
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
Follow up
D A test-of-cure is not necessary when treatment with doxycycline or
azithromycin has been completed, unless symptoms persist or reinfection is suspected. Test-of-cure is however recommended after 4
weeks for infections in pregnant women, or when erythromycin was
used. Non-culture tests (e.g. NAAT) done within 4 weeks of
completing treatment may yield false positive tests due to persistence
of chlamydial antigens.9
Grade D, Level 4
51
51
D Sex partners of symptomatic male patients within the last 60 days
(or the most recent sex partner if the last contact was >60 days) should
be screened and treated for chlamydial infection.9
Grade D, Level 4
D Sex partners of asymptomatic male patients and of females within
the last 90 days (or the most recent sex partner if the last contact was
>90 days) should be screened and treated for chlamydial infection.9
Grade D, Level 4
3.8
Treatment of non-gonococcal urethritis (NGU)
Recommended regimens
(See treatment of Chlamydia trachomatis above).
D Sex partners of men with non-gonococcal urethritis (NGU) within
the last 60 days should be screened and treated. These partners should
also be examined to exclude other associated STI.9
Grade D, Level 4
At least 30% of consorts of men with NGU have chlamydial
infections of the cervix and such women are at risk of developing
upper genital tract infections, which are often asymptomatic and have
the potential sequelae of ectopic pregnancy, infertility and chronic
pelvic inflammatory disease.90
Management of recurrent or chronic NGU
This is empirically defined as persistent or recurrent symptoms of
urethritis occurring 4 to 6 weeks following treatment of acute NGU
and occurs in up to 30% of patients. There is no consensus of opinion
for either the diagnosis or the management of this condition.
Persistent chlamydial infection is only rarely detected. There is
evidence that ureaplasmas and M. genitalium may be important in the
aetiology of chronic NGU. Some men with recurrent or persistent
NGU are anxious, obsessional, and hypochondriacal. There may also
52
52
be an association with guilt over a perceived inappropriate sexual
episode.
- D Obtain objective evidence of urethritis, e.g. presence of
urethral discharge or pus cells on urethral smear. If patient has no
objective evidence, consider reassurance only.
- Exclude drug adherence failure or re-infection from untreated
partner or a new partner.
- Consider referral to a specialist for further evaluation.9
Grade D, Level 4
3.9
Vaginal discharge
Vaginal discharge is the commonest genital symptom in women. The
causes can be physiological or pathological.
3.9.1
Physiological vaginal discharge
Pre-menopausal women may have normal physiological discharge
that is cyclical in nature. The quantity of physiological discharge will
vary from minimal during parts of the cycle but profuse at other times.
The causes of physiological vaginal discharge are listed in Table 1.
B In women of reproductive age complaining of vaginal discharge the
commonest cause is physiological, but infective and other causes
should be excluded.91,92
Grade B, Level 2++
53
53
Table 1
Causes of vaginal discharge
1.
Physiological
Hormonal factors:
Variation during the menstrual cycle
Hormonal contraception
Pregnancy
Lactational atrophic vaginitis
Postmenopausal atrophic vaginitis
Sexual arousal
2.
Pathological
Infective causes
Vaginal causes (Commonest causes):
Bacterial Vaginosis
Vulvovaginal candidiasis
Trichomonas vaginalis
Cervical causes:
Non-infective Inflammatory causes:
Irritant contact dermatitis e.g. topical medications, lubricants
Allergic contact dermatitis e.g. latex
Other causes of discharge:
Foreign body e.g. retained tampon, intrauterine contraceptive
device
Cervical polyps
Genital (Cervical, Endometrial or vaginal) neoplasia
Endometritis
3.9.2
How should a woman with vaginal discharge be
investigated?
When a woman presents with a complaint of vaginal discharge, her
clinician should consider if and when investigations are required.
B A spontaneous complaint of abnormal vaginal discharge is most
commonly due to a vaginal infection, and rarely, it may be the result
of mucopurulent STI-related cervicitis. The symptom of abnormal
vaginal discharge is highly indicative of vaginal infection, but poorly
predictive for cervical infection. To ensure a cost-effective approach,
54
54
risk assessment should therefore be done before investigations and
treatment is provided.91,92
Grade B, Level 2++
B Where resources permit, one should consider the use of laboratory
tests to screen women with vaginal discharge. Such screening could
be applied to all women with discharge as well as to those with a
positive risk assessment.91,92
Grade B, Level 2++
GPP Investigation of a woman with vaginal discharge is indicated if
(Table 2):
(STI).
5. She is within 3 weeks of insertion of intrauterine contraceptive
device.
6. Requested by the patient.
GPP
Table 2
Investigations for vaginal discharges
Site
Vulval fissures
and erythema
Vagina
Cervix
Investigations
Microscopy for yeasts
Culture for yeasts
Herpes simplex virus (if multiple vesicles or
ulcers present)
Wet preparation to detect Trichomonas
vaginalis (posterior fornix)
Gram stain to detect clue cells and yeasts
(lateral walls)
Culture for Trichomonas vaginalis and yeasts
(lateral walls and posterior walls)
Amine ‘sniff’ test (if available)
Vaginal pH (if available)
Gram-stain for pus cells, Gram-negative
intracellular diplococci
Culture Neisseria gonorrhoeae
Nucleic-acid amplification test (NAAT) for
55
55
The presence of vaginal discharge, in itself, is a poor predictor of
STI.93
A sexual history should be taken to assess the risk of STI when the
patient has vaginal discharge.
Risk factors of STIs are: age <25 years, change of new sexual partner
in the last year or more than one sexual partner in the last year.74-76
B Not all women with vaginal discharge require investigation.
Empirical treatment can be given after taking a clinical and sexual
history if:
1. The woman is at low risk of STI.
2. She has no symptoms to suggest upper genital tract infection.
3. She can return for follow-up if symptoms do not resolve.25
Grade B, Level 2++
B A woman of reproductive age complaining of vaginal discharge
should be investigated if94:
(STI).
5. She is within 3 weeks of insertion of intrauterine contraceptive
device.
6. Investigation is requested by the patient.
Grade B, Level 2++
3.9.3 Infections and vaginal discharge
Vaginal infections due to bacterial vaginosis, Trichomoniasis
vaginalis and vulvovaginal candidiasis commonly present with
vaginal discharge (Table 3).
B The major causes for vaginal discharge include candidiasis,
bacterial vaginosis, trichomoniasis, Chlamydia trachomatis and
gonococcal infection. Depending on the physician assessment of the
patient’s risk factors, syndromic management may be directed against
one or all of these common causes.91,92
Grade B, Level 2++
56
56
3.9.3.1
Bacterial vaginosis
Bacterial vaginosis is characterised by an overgrowth of
predominantly anaerobic organisms (Gardnerella vaginalis,
Mycoplasma hominis and Mobiluncus species) in the vagina, leading
to replacement of lactobacilli and an increase in pH from less than 4.5
to as high as 7.0. Spontaneous onset and remission of bacterial
vaginosis can occur. Whilst bacterial vaginosis is not considered a
sexually transmitted disease, it is more common amongst sexually
active than non-sexually active women.95
Bacterial vaginosis presents with complaints of an unpleasant fishy
smelling vaginal discharge; however, it can be asymptomatic.
Bacterial vaginosis is not associated with itch, soreness or irritation. A
malodorous, white-grey, thin homogeneous discharge is often visible
and adherent to the introitus.
Diagnosis is made by the Amsel criteria or with a Gram stained
vaginal smear (Hay/Ison or Nugent Criteria).
Amsel Criteria96
Bacterial vaginosis is confirmed on the basis of fulfillment of three or
more of the four Amsel criteria:
1. Thin, homogenous, white vaginal discharge
2. Vaginal pH >4.5
3. Clue cells on microscopy of wet mount
4. Positive amine test (addition of potassium hydroxide to a wet
preparation of vaginal secretion releases a fishy odour).
Hay / Ison Criteria97
Grade 1 (Normal): Lactobacillus morphotypes predominate.
Grade 2 (Intermediate): Mixed flora with some Lactobacilli present,
but Gardnerella or Mobiluncus morphotypes also present
Grade 3 (bacterial vaginosis): Predominantly Gardnerella and/or
Mobiluncus morphotypes. Few or absent Lactobacilli.
Nugent Criteria98
Nugent score is derived from estimating the relative proportions of
bacterial morphotypes to give a score between 0 and 10. A score of <
57
57
4 is normal and 4-6 is intermediate. Bacterial vaginosis is diagnosed if
Nugent score is > 6.
Note:
1. Menses, semen, cervical secretions or douching may affect the
pH, a weak positive “sniff test” may be produced by menstrual
blood or semen.
2. Isolation of Gardnerella vaginalis cannot be used to diagnose
bacterial vaginosis because it can be cultured from the vagina of
normal women.
Special groups
Pregnancy
In pregnancy, bacterial vaginosis is associated with late miscarriage,
preterm delivery, preterm premature rupture of membranes, and
postpartum endometritis.99-102
Three randomized controlled studies showed a reduction in the
incidence of preterm birth following screening for and treatment of
bacterial vaginosis with metronidazole in women with a history of
prior idiopathic preterm birth or second trimester loss. Unfortunately,
the studies used different treatment regimes.103-105
Some randomized controlled studies and systematic reviews showed
that treatment was not beneficial or even harmful and increased the
rate of preterm delivery in both low-risk as well as high-risk
groups.106-108
Thus, current evidence is insufficient to evaluate the balance of
benefits and harms of screening for bacterial vaginosis in pregnant
women at high risk for preterm delivery. In asymptomatic pregnant
women at high risk for preterm delivery, studies are lacking, and
evidence is therefore poor, for the benefits or harms of screening for
bacterial vaginosis.
Women undergoing elective termination of pregnancy (TOP)
Bacterial vaginosis is associated with post-TOP endometritis and
pelvic inflammatory disease (PID). Screening and treating bacterial
58
58
vaginosis reduce the incidence of subsequent
PID.109-111
Table 3
Symptoms
Signs
Vaginal pH
endometritis and
Symptoms and signs of common infections for
vaginal discharge
Bacterial vaginosis
Vulvovaginal
candidiasis
Trichomonas
vaginalis
Thin homogeneous
discharge
Thick curdish
discharge
Scanty to profuse
yellow greenish
discharge
Fishy smell
Non-offensive smell
Offensive smell
No itch
Vulval itch or soreness
Vulval itch
Discharge coating
vagina
Vulval erythema
Vulva and vagina
inflammation
No vulval
inflammation or
erythema
Presence of satellite
lesions
“Strawberry”
cervix (seen in 2%
cases)
4.5
< 4.5
4.5
Treatment of bacterial vaginosis
Indications for treatment:
1. A All symptomatic women with bacterial vaginosis, pregnant or
non pregnant.112,113
Grade A, Level 1+
2.
A Asymptomatic women with bacterial vaginosis before surgical
procedures. 112,113
Grade A, Level 1+
General Measures
D Patients with bacterial vaginosis should avoid vaginal douching,
use of shower gels, antiseptic agents or shampoo in the bath.112
Grade D, Level 3
59
59
Recommended regimens for bacterial vaginosis:112,113
1.
Clindamycin site-released (SR) cream 2% (5 g) intravaginally x
single application.
OR
2.
OR
3.
OR
OR
6.
Grade A, Level 1+
A Metronidazole pessary (500 mg) intravaginally bid x 7 days or
daily x 14 days.
5.
Grade A, Level 1+
A Metronidazole gel 0.75% (5 g) intravaginally daily x 5 days.
OR
4.
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
Note:
1. A Metronidazole 2 g orally single dose therapy is the least
effective for bacterial vaginosis and is no longer recommended.106
Grade A, Level 1+
2.
3.
4.
Intravaginal metronidazole gel and clindamycin cream have
similar efficacy.
Metronidazole is less active against lactobacilli than clindamycin.
However, clindamycin is more active than metronidazole against
most of the bacteria associated with bacterial vaginosis.
Clindamycin reduces vaginal Mobiluncus to a greater extent than
metronidazole.114-116
Clindamycin vaginal creams and suppositories may be oil-based
and might weaken latex condoms.117
60
60
Bacterial vaginosis in pregnancy
A If bacterial vaginosis causes vaginal discharge in pregnancy, it
should be treated as for non-pregnant women.118
Grade A, Level 1+
Recommended regimens for pregnant women:119
1.
Clindamycin-sustained released
(SR)
OR
2.
OR
3.
2%
(5
g)
Grade A, Level 1+
Grade A, Level 1+
A Metronidazole pessary (500 mg) intravaginally bid x 7 days or
daily x 14 days.
OR
4.
cream
Grade A, Level 1+
A Metronidazole 400 mg orally bid x 7 days. (Avoid in first
trimester*).
Grade A, Level 1+
Note:
1. *Metronidazole crosses the placental barrier. Although it has
been given to pregnant women without apparent complication or
teratogenicity, it is advisable to withold oral or vaginal
metronidazole during the first trimester of pregnancy.
2. In three trials, intravaginal clindamycin cream was administered
at 16-32 weeks’ gestation, and an increase in adverse events (e.g.,
low birth-weight and neonatal infections) was observed in
newborns. Therefore, intravaginal clindamycin cream should only
be used during the first half of pregnancy.99,120,121
Recurrent bacterial vaginosis
Recurrence of bacterial vaginosis occurs within 3 months of treatment
in 15-30% of women. There are few published studies evaluating the
optimal approach to women with frequent recurrences of bacterial
vaginosis.122
61
61
Suppressive regimes may be considered but evidence to support their
effectiveness is limited.
Suggested suppressive therapy for recurrent bacterial
vaginosis:123
1.
A Metronidazole gel 0.75% (5 g) twice weekly for 4-6 months.
OR
2.
Grade A, Level 1+
C Metronidazole 400 mg orally bid for 3 days at the start and end
of menstruation.
Grade C, Level 2+
Suggested maintenance regime for recurrent bacterial vaginosis:
B Acetic acid vaginal gel use at the time of menstruation and
following unprotected sexual intercourse to maintain acidic vaginal
pH.123
Grade B, Level 2+
Follow up
D Follow-up is not necessary if symptoms resolve. A test of cure is
not required.9
Grade D, Level 4
No clinical counterpart is recognised in males and screening and
treatment has not shown to be beneficial for the male partner.
Although some studies reported a high incidence of bacterial
vaginosis in female partners of lesbian women with bacterial
vaginosis, no studies have as yet investigated the value of treating
partners of lesbian women simultaneously.124,125
3.9.3.2
Vulvovaginal candidiasis
Vulvovaginal candidiasis is caused by Candida albicans in the
majority of cases (80-92%). The non-albicans species include
C.glabrata, C.tropicalis, C.krusei, C.parapsilosis, and Saccharomyces
cerevisiae.126,127
62
62
Vulvovaginal candidiasis commonly presents with vulval itch or
soreness with a curd-like vaginal discharge. Occasionally, it can be
associated with superficial dyspareunia or external dysuria. Clinically,
the woman may have signs of erythema and excoriation over the vulva
or vagina with a curdy discharge. Satellite lesions may be seen.
The risk factors include pregnancy, diabetes mellitus, prolonged
corticosteroid therapy, antibiotics treatment, and immunosuppression.
Laboratory tests include Gram-stain or wet mount (saline or 10%
Potassium hydrochloride) of swabs from the vulva/vaginal wall which
reveal budding yeast cells and pseudohyphae (sensitivity 60%),
vaginal pH 4-4.5 and culture on Sabouraud medium.
Note:
1. Isolation of Candida species in the absence of symptoms and
signs does not suggest infection and is not an indication for
treatment as 10-20% of women during reproductive years may be
colonized with Candida species.
2. None of the above symptoms or signs is pathognomonic for
vulvovaginal candidiasis.
3. The symptoms and signs are no guide to the underlying causative
species.128,129
Treatment of candidiasis
Treatment is indicated for symptomatic patients.
D Avoid local irritants (e.g. perfumed vaginal douch), scented pantyliners and tight fitting synthetic clothing.130,131
Grade D, Level 4
Treatment for uncomplicated acute vulvovaginal candidiasis
A Both vaginal or oral antifungals (azoles) can be used in the
treatment of uncomplicated acute vulvovaginal candidiasis 32
Grade A, Level 1+
Recommended regimens for uncomplicated acute vulvovaginal
candidiasis:132
1.
A Butoconazole1-sustained released (SR) cream site 2% (5 g)
63
63
Grade A, Level 1+
OR
2.
A Clotrimazole pessary 200 mg intravaginally daily x 3 days or
100 mg or 1% cream (5 g) intravaginally daily x 7 days or 500 mg
x single application.
OR
3.
A Fluconazole 150 mg orally single dose.
OR
4.
A Itraconazole 200 mg orally bid x 1 day.
OR
6.
Grade A, Level 1+
A Isoconazole pessary 600 mg intravaginally x single application.
OR
5.
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
A Miconazole pessary 200 mg intravaginally daily x 3 days or 100
mg or 2% cream (5 g) intravaginally daily x 7 days.
OR
7.
A Nystatin pessary 100,000 U daily x 14 days.
Grade A, Level 1+
Grade A, Level 1+
Note:
1. All topical and oral azole therapies give a clinical and
mycological cure rate of 80-90% in uncomplicated vulvovaginal
candidiasis. Nystatin preparations give 70-90% cure rate.
2. The treatment choice is the personal preference, availability and
affordability as well as familiarity of the clinician with the
treatment.
3. Topical azole creams and suppositories may be oil-based and
might weaken latex condoms.117
4. Topical azole treatment may cause vulvo-vaginal irritation and
this should be considered if symptoms worsen.129,133-136
Follow up
GPP Follow-up is not necessary if symptoms resolve. A test of cure
is not required.132
GPP
64
64
There is no evidence to support the treatment of asymptomatic male
sexual partners in either episodic or recurrent vulvovaginal
candidiasis.137,138
Recurrent vulvovaginal candidiasis
This is defined as 4 or more episodes of symptomatic vulvovaginal
candidiasis in a year. There may be partial resolution of symptoms
between episodes. Positive microscopy or a moderate/heavy growth of
Candida should be documented on at least two episodes.
5% of women with acute vulvovaginal candidiasis will develop
recurrent vulvovaginal candidiasis. It is usually due to C albicans
although C.glabrata and other non-albicans species are observed in
10-20% of patients with recurrent vulvovaginal candidiasis.139,140
Patients must be evaluated for any predisposing factors. These include
uncontrolled diabetes mellitus, immunosuppression, high oestrogen
state (e.g. use of oral contraceptive pill and hormonal replacement
therapy), disturbance of normal vagina flora (e.g. use of broadspectrum antibiotics) and corticosteroid use.
Treatment of recurrent vulvovaginal candidiasis
GPP Clinicians should be aware of psychosexual problems and
depression, which can occur in women with recurrent vaginal
infections.
GPP
The principle of therapy involves an induction regimen to ensure
clinical remission, followed immediately by a maintenance regimen.
Recommended regimens for recurrent vulvovaginal
candidiasis:132,138-140
Induction regimens
1.
A Fluconazole 150 mg orally every 72 hours x 3 doses.
OR
65
65
Grade A, Level 1+
2.
C Topical imidazole therapy x 7-14 days according to
symptomatic response.
Grade C, Level 2+
Maintenance regimens
1.
B Clotrimazole pessary 500 mg intravaginally once a week or 200
mg intravaginally twice a week.
OR
2.
B Fluconazole 150 mg orally once a week.
Grade B, Level 2++
Grade B, Level 2++
Note:
1. B Maintenance therapy should last 6 months. 90% of women
should remain disease-free during treatment.132,139,140
Grade B, Level 2++
2.
C For women who have relapses between doses, consider twiceweekly 150 mg fluconazole or 50 mg fluconazole daily.132,139,140
Grade C, Level 2+
D Monitor the liver function test when the woman is on regular oral
azole treatment.141
Grade D, Level 4
Alternative treatment for vulvovaginal candidiasis.
Probiotics/Lactobacillus
There is insufficient evidence to support the use of oral or vaginal
lactobacillus to prevent vulvovaginal candidiasis although there are
anecdotal reports of benefit.142,143
Special groups
Candidiasis in pregnancy
Asymptomatic colonization with Candida species is more common
(30-40%).
Colonisation with Candida species is not associated with low birth
weight or premature delivery. Thus, no treatment is necessary for
asymptomatic colonization.
66
66
B Symptomatic candidiasis in pregnancy should be treated with
topical azole therapy only. Longer courses (seven days) are
recommended. Oral azole therapy is contraindicated.144-146
Grade B, Level 2+
Candidiasis in diabetes mellitus
Glycaemic control should be optimized. There is an increased
prevalence of non-albicans species, in particular C glabrata.
For treatment of symptomatic women with C glabrata isolated, boric
acid 600 mg intravaginal suppository once a day for 14 days is as
effective as a single dose of fluconazole 150 mg, and either may be
used.145-149
Candidiasis in HIV infection
Vulvovaginal candidiasis occurs more frequently and with greater
persistence in women with HIV infection. Treat with conventional
methods.150,151
Non-albicans Candidiasis
The majority of non-albicans infection is due to Candida glabrata and
is susceptible to available azoles. Candida krusei is intrinsically
resistant to fluconazole.
The optimal treatment of non-albicans vulvovaginal candidiasis
remain unknown. Non-albicans infection may require longer courses
(7-14 days).
Treatment
C Nystatin pessaries or nonfluconazole azole drug (oral or topical)
are the first line treatment for non-albicans infection.
OR
Grade C, Level 2+
C Consider Amphotericin B vaginal suppositories 50 mg once a day
for 14 days.152-154
Grade C, Level 2+
67
67
3.9.3.3
Trichomoniasis
Trichomoniasis is caused by Trichomonas vaginalis, a protozoan that
causes vaginitis in women. It infects the vagina, urethra and
paraurethral glands. In adults, transmission is almost exclusively
sexually transmitted.
10-50% of infected women can be asymptomatic. Predominant
symptoms are yellow-green and offensive discharge, vulval itch or
dysuria.
On examination the vulva may be erythematous or excoriated, the
vagina inflamed, and small cervical haemorrhages and ulcers can give
the classical appearance of the “strawberry cervix” which occurs in
2% of infected patients.155-157
Laboratory tests include direct microscopy of the wet mount of
vaginal secretions mixed with normal saline (sensitivity 70%). A swab
taken from the posterior fornix of vagina and cultured on FeinbergWhittington media is the most sensitive (sensitivity > 90%) and
specific for trichomoniasis.158-160[0]
D Sexual contacts in the preceding 60 days should be traced, screened
and treated on epidemiologic grounds. If the last sexual exposure was
>60 days, the patient’s most recent partner should be treated.9
Grade D, Level 4
D Patients should be advised to avoid sexual intercourse (including
oral sex) until they and their partner(s) have completed treatment and
follow-up.9
Grade D, Level 4
D Screening for coexisting sexually transmitted infections should be
undertaken in both the patients and their partners.9
Grade D, Level 4
C Women should be informed that T. vaginalis is a STI and partner
management and treatment is recommended for all partners in the last
2 months.161
Grade C, Level 2+
68
68
Treatment of trichomoniasis
Both symptomatic and asymptomatic patients should be treated.
Recommended regimen for trichomoniasis:161
1.
A Metronidazole 2 g orally x single dose.
OR
2.
OR
3.
Grade A, Level 1+
Grade A, Level 1+
Grade A, Level 1+
Note:
1. D Metronidazole gel is not recommended because it is less
efficacious (< 50%).72
Grade D, Level 4
2. The recommended metronidazole regimes have resulted in cure
rates of 90-95%.
Trichomoniasis in pregnancy
Trichomonas infection has been associated with premature rupture of
the membranes, preterm delivery and low birthweight. However, data
do not suggest that metronidazole treatment results in a reduction in
perinatal morbidity.162,163
D Although the use of metronidazole in pregnancy has not been
shown to be teratogenic or mutagenic in all stages of pregnancy or
breastfeeding, caution should be advised for use in the first trimester.
Metronidazole pessaries may be used to provide symptomatic relief
but have lower cure rates than the oral regimes.72
Grade D, Level 4
D Treatment of Trichomonas vaginalis relieves symptoms of vaginal
discharge in pregnant women and might prevent respiratory or genital
infection of the newborn and further sexual transmission. Clinicians
should counsel patients regarding the potential risks and benefits of
treatment.72
Grade D, Level 4
69
69
A It is reasonable to delay therapy in asymptomatic pregnant women
until after 37 weeks’ gestation. In addition, these pregnant women
should be provided careful counseling regarding condom use and the
continued risk of sexual transmission.164,165
Grade A, Level 1+
Follow up
A Follow-up is unnecessary for asymptomatic patients. Patients with
persistent symptoms should be retreated with metronidazole 400 mg
orally bid for 7 days.161
Grade A, Level 1+
A If treatment failure occurs repeatedly, the patient can be treated
with high dose oral metronidazole 2 g daily for 3 days.161
Grade A, Level 1+
70
70
44
GPP Doctors should consider efficacy, adverse side effects, dosing
frequency, and cost to the patient when recommending treatments. For
compliance issues, single dose therapies are generally recommended.
GPP
B Male patients complaining of urethral discharge and/or dysuria
should be examined for discharge. The major pathogens causing
urethral discharge are Neisseria gonorrhoeae and Chlamydia
trachomatis. In the syndromic management of a patient with urethral
discharge, treatment should adequately cover these two organisms and
has been found to be cost-effective. Where reliable laboratory
facilities are available, a distinction may be made between the two
organisms.166,167
Grade B, Level 2++
71
71
55
Clinical quality improvement
The following clinical quality improvement parameters, based on
recommendations in these guidelines, are proposed:
1.
Every patient presenting with genital discharges and/or ulcers
should have a sexual history taken and sexual risk assessment
evaluation (pg 27).
2.
All patients should be educated and counseled on their condition,
and be encouraged to adopt safer sexual behaviours (pg 29).
3.
Patients with gonorrhoea should be treated with the recommended
antibiotics, and specifically should not be treated with quinolones
(pg 49).
4.
Patients with gonorrhoea should be concurrently given treatment
for Chlamydia trachomatis (pg 49).
5.
Patients with syphilis should be treated with parenteral penicillin
unless there is a contraindication (pg 37).
6.
Partner notification should be encouraged in all patients
diagnosed with an STI (39).
72
72
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Self-assessment
(MCQs)
Self-assessment
(MCQs)
After reading the Clinical Practice Guidelines, you can claim one CME
point under Category III (Self-Study) of the SMC Online CME System.
Before you login to claim the CME point, we encourage you to evaluate
whether you have mastered the key points in the Guidelines by completing
this set of MCQs. This is an extension of the learning process and is not
intended to “judge” your knowledge and is not compulsory. The answers
can be found at the end of the questionnaire.
Instruction: Choose “True” or “False.
1.
Genital ulceration:
A) increases the risk for HIV acquisition
B) occurs in lichen planus
C) is most commonly caused by Treponema pallidum
D) may occur as a result of a drug allergy
2.
Regarding genital herpes:
A) it is transmitted only when the patient is
symptomatic
B) culture specimens should be frozen at 0qC before
dispatch to the laboratory
C) caesarian section should be routinely offered to all
pregnant women with a history of the disease
D) acyclovir should not be used in pregnancy
3.
In primary syphilis:
A) the presence of a painful genital ulcer excludes the
diagnosis
B) a persistently positive TPHA test after treatment
indicates failure of therapy
C) intramuscular benzathine penicillin 2.4 MU single
dose is the treatment of choice
D) doxycycline is an alternative to intramuscular
penicillin injection in pregnancy.
90
90
True
False

4.
5.
6.
7.
A 25-year-old male complains of clear urethral
discharge 3 days after unprotected sexual intercourse
with a sex worker. Possible causes include:
A) Chlamydia trachomatis
B) Herpes simplex virus
C) Trichomonas vaginalis
D) Ureaplasma urealyticum
A) causes symptomatic vaginal discharge in 80% of
infected women
B) may lead to an acute epididymo-orchitis
C) is diagnosed by presence of gram-negative
diplococci in a urethral smear
D) sex partners of symptomatic male patients within
the last 60 days should be screened and treated for
infection
A 20-year-old female presents with a 1-week history of
an itchy vaginal discharge. She has had 2 different
sexual partners in the past 6 months and requests STI
screening. The following investigations should be done:
A) culture for Neisseria gonorrhoeae
B) blood test for Chlamydia trachomatis IgG
C) Neisseria gonorrhoeae Complement fixation test
D) Culture for Trichomonas vaginalis
A 30-year-old male presents with a 3-day history of a
profuse, purulent urethral discharge after unprotected
sexual intercourse with a casual female partner. He
declines any investigations. You should treat him with:
A) ciprofloxacin 500 mg bid for 3 days
B) intramuscular ceftriaxone 250 mg single dose
C) intramuscular benzathine penicillin 2.4MU single
dose
D) azithromycin 1g orally single dose T
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91
True
False

8.
Regarding bacterial vaginosis:
A) it occurs only in sexually active women
B) it is associated with preterm delivery
C) it is recommended that all symptomatic women be
treated
D) male partners of patients should be routinely
screened and treated
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92
True
False

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93
Answer
1 A)
1 B)
1 C)
1 D)
T
T
F
T
2 A)
2 B)
2 C)
2 D)
F
F
F
F
3 A)
3 B)
3 C)
3 D)
F
F
T
F
4 A)
4 B)
4 C)
4 D)
T
T
T
T
pg 27
pgs 30-32,36
pgs 36,37,40
pg 44
5 A)
5 B)
5 C)
5 D)
F
T
F
T
6 A)
6 B)
6 C)
6 D)
T
F
F
T
7 A)
7 B)
7 C)
7 D)
F
T
F
T
8 A)
8 B)
8 C)
8 D)
F
T
T
F
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pgs 45-47,52
pg 55
pgs 11-14
pgs 57-59,62
Workgroup
Workgroup members
members
The members of the workgroup, who were appointed in their personal
professional capacity, are:
Chairman
Dr Tan Hiok Hee
Head, Dept of STI Control Clinic /
Senior Consultant Dermatologist
National Skin Centre
Members
Prof Chan Kum Wah, Roy
Senior Consultant and Director,
National Skin Centre /
Adj Professor, Dept of
Epidemiology and Public Health,
Yong Loo Lin School of Medicine
Dr Priya Sen
Consultant, National Skin Centre /
Deputy Head, Dept of STI Control
Clinic
Dr Chio Tze-Wei, Martin
Consultant, National Skin Centre
Dr Tan Thiam Chye
Assistant Professor,
Duke-NUS Graduate Medical
School /
Associate Consultant,
Dept of Obstetrics and Gynaecology
KK Women's and Children's
Hospital
A/Prof Goh Lee Gan
Associate Professor,
Dept of COFM
Yong Loo Lin School of Medicine /
President, College of Family
Physicians, Singapore
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95
Dr Ngan Cheng Lai, Cecilia
Senior Consultant Microbiologist
Immunology & Serology Section
Dept of Pathology
Singapore General Hospital
Dr Lim Fong Seng
Family Physician
NHG Polyclinics
Dr Cheong Wai Kwong
Consultant Dermatologist
Specialist Skin Clinic (S) Pte Ltd
Dr Asok Kurup
Senior Consultant
Department of Infectious Diseases
Singapore General Hospital
Dr Toh Khai Lee
Senior Consultant Urologist &
Deputy Head
Dept of Urology
Tan Tock Seng Hospital
Subsidiary editors:
Dr Pwee Keng Ho
Deputy Director (Health Technology Assessment)
Health Services Research & Evaluation Division
Ministry of Health
Ms Celeste Ong
Assistant Manager (Health Technology Assessment)
Health Services Research & Evaluation Division
Ministry of Health
Acknowledgement:
Dr Edwin Chan Shih-Yen
Head of Evidence-Based Medicine
and
Director of the Singapore Branch, Australasian Cochrane Centre
Clinical Trials & Epidemiology Research Unit
Dr Pradeep Paul
Clinical Trials & Epidemiology Research Unit
Singapore Branch of the Australasian Cochrane Centre
95
96
Management of
Genital Ulcers
and Discharges
Ministry of Health, Singapore
16 College Road
Singapore 169854
TEL (65) 6325 9220
FAX (65) 6224 1677
WEB www.moh.gov.sg
ISBN 978-981-08-3340-4
Academy of
Medicine,
Singapore
Chapter of Dermatologists
College of Physicians,
Singapore
College of Obstetricians
and Gynaecologists,
Singapore
College of Family
Obstetrical &
Physicians,
Gynaecological
Singapore
Society of Singapore
Dermatological
Society of
Singapore
May 2009