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Transcript
National Medicines
Information Centre
VOLUME 18
NUMBER 2
2012
ST. JAMES’S HOSPITAL • DUBLIN 8
TEL 01-4730589 or 1850-727-727 • FAX 01-4730596 • www.nmic.ie
update on sexually transmitted infections
The incidence of sexually transmitted infections (STIs), which are a major cause of morbidity and
mortality worldwide, is increasing
It is important to consider sexual health in all patients and to ask about sexual history in patients with
risk factors for STIs
Patients frequently have >1 STI present; the diagnosis of a STI should prompt a search for others
that may be asymptomatic
Partner notification is an important aspect of STI management, which may require referral to a specialist service
INTRODUCTION
Sexually transmitted infections (STIs) present a major public health problem and are a major cause of acute illness, infertility,
long-term disability and death worldwide.1-3 Early diagnosis and treatment of STIs can cure and prevent complications including
pelvic inflammatory disease (PID), urethritis, infertility, arthritis and meningitis.3,4 The global incidence of STIs is rising;1,5 since
the 1990s the EU (including Ireland) has experienced significant increases in the incidence of STIs, especially genital chlamydia,
gonorrhoea and syphilis.2,6-8 STIs are frequently asymptomatic and an additional concern is that there is increasing antimicrobial
resistance to some STIs, in particular gonorrhoea.3,9-13 The increased incidence of STIs may reflect an increase in unsafe sexual
behaviour, however it may also be due to increased testing, better diagnostics and more reporting.8 Sexual health is an important
aspect to consider for all patients. In 2011, 11,000 cases of STIs were notified in Ireland, as follows: genital chlamydia
(51%), ano-genital warts (16%), genital herpes simplex (9%), gonorrhoea (7%) syphilis (6%), trichomoniasis (0.5%) and
non-specific urethritis (10%).6 HIV became a notifiable disease in September 2011.14 This bulletin will review the commonest
notifiable STIs; a future bulletin will review the management of HIV.
Risk factors for STIs
Certain patient groups are more at risk of acquiring a STI (see Table 1). A recent Irish study found that there was a lack of
awareness amongst young people (17-34 years) of symptoms suggestive of STIs, and that there were significant levels of high
risk behaviour.15 While young age is a risk factor, it is important to be aware that STIs are not only confined to young people.16
Healthcare professionals often do not discuss risky sexual behaviour and STI prevention with middle-aged and older adults.4 The
incidence of STIs in those >50 years, has more than doubled in the last decade,16,17 due to factors including changing attitudes in
society, new relationships, international travel, the use of drugs for erectile dysfunction and the misconception that condoms are
only for contraception.4,5,16-18 Patients frequently have >1 STI present; the diagnosis of a STI should prompt a search for
others that may be asymptomatic.5
Table 1: Risk factors for acquiring a STI 5
•
•
•
•
•
Aged <25 years
More than 2 sexual partners in the previous year
A previous STI
No/infrequent/inconsistent condom use
Living in an area of high STI prevalence (generally, urban areas)
• Visiting an area of high STI prevalence (e.g. engaging in unprotected
sex in certain overseas countries)
• Men who have sex with other men
• Certain minority ethnic groups
• Those who buy or sell sex
• The sexual partners of all of the above
Assessment for STIs
While many patients attend specialist STI clinics for testing, patients with STIs may also present to non-specialist settings and all
clinicians should be aware of the appropriate management of a patient with a STI.5 Patients with STIs are also seen in primary
care;1,2 services may range from testing and referring positive cases to specialist services, to managing uncomplicated cases
depending on the clinical situation.5 Certain STIs (in particular syphilis) should be referred to a specialist setting.19 It is also
important to note that partner notification is an important aspect of STI management; this may require referral of the patient
to a specialist service, (which has a multidisciplinary structure).
A sexual health history should be incorporated into the evaluation of patients, as detailed in Table 2.19
Table 2: Sexual history19
Symptom history
It is important to think of the possibility of STIs. There are many
symptoms of STIs, which include the following:
Men
• Urethritis can present with urethral discomfort/itch, dysuria,
discharge, epididymo-orchitis, reactive arthritis, conjunctivitis
(autoinoculation)
Women
• Cervicitis can present with intermenstrual bleeding, post coital
bleeding, deep dyspareunia, lower abdominal pain, ophthalmia
neonatorum
• Pelvic inflammatory disease – as above plus ectopic pregnancy
and infertility
• Vaginal infections – vaginal discharge, itch, soreness
Medical history
• Past medical history (including STIs)
• Medication (including illicit drugs)
• Allergy
• Obstetric/gynaecological history for women
Partner history
• When was the last sexual encounter?
• Who with? (traceable or not? male or female? overseas?)
• What sort of sex (oral, vaginal, anal?)
• Were condoms used for all contacts?
• Does the partner have a history of previous STIs and/or any
symptoms?
• How many partners over last 3 months?
Patients with STIs can present in a variety of ways; they may be symptomatic or asymptomatic presenting with an
unrelated problem (belonging to a high risk group) or requesting to be tested for a STI.5 Contraceptive consultations
provide an excellent opportunity to enquire about sexual health and to consider offering STI testing. Taking a sexual
history involves personal and sensitive issues that can cause stress to the patient, and requires a sensitive approach.
Examination should include the genital area and the oral and perianal areas, as indicated by the patients’ history. For
women with a suspected STI, a vaginal examination using a speculum should be undertaken (a self obtained vaginal swab
can be used to test for chlamydia and gonorrhoea in asymptomatic women).20 Clinicians should consider the need for a
chaperone during an intimate examination.
Investigations include testing for (1) chlamydia, gonorrhoea and trichomonas in patients with genital discharge, (2)
syphilis and herpes in patients with genital ulcers and (3) chlamydia, gonorrhoea, syphilis, HIV and hepatitis B in
asymptomatic patients with risk factors for STIs.21 Patients should be informed of the tests being undertaken. Nucleic
acid amplification tests (NAATs) have been developed in recent years.5 These tests detect small amounts of the RNA and
DNA of organisms and can be extremely sensitive and specific. Unlike culture methods they do not require organisms to
remain viable, therefore urine samples or self-obtained swabs can be stored and transported to the laboratory at ambient
temperatures. Contact should be made with the local laboratory to determine which tests are available and the transfer
arrangements required.
management of STIs
The diagnosis of a STI often causes considerable distress to the patient and management should include the following:
information on the natural history of the infection, advice on how the STI is transmitted, the complications of not treating
the infection, the importance of their partners being evaluated and treated and the need to abstain from sexual intercourse
(including oral) until therapy is completed.19,20 Patients and their partner/s should be tested for other STIs including
HIV and hepatitis B. Every STI consultation is an opportunity for preventive education including the importance of
the use of condoms to prevent STIs and that the fewer the number of sexual partners, the lower the risk of STI. Table
3 summarises the clinical manifestations, diagnosis and treatment of the common STIs. In addition, vaccination for
hepatitis A and B should be offered to patients who are intravenous drug users and men who have sex with men (MSM).
Non-specific urethritis is a diagnosis of exclusion after gonorrohoea and chlamydia have been excluded; many organisms
can cause it including Trichomonas vaginalis, ureaplasma, herpes and mycoplasma.19
Medical practitioners are required to notify STIs to the Medical Officer of Health/Director of Public Health for the
area of residence of the patient, using the notification of infectious diseases form (available on www.hpsc.ie). The Society
for the Study of Sexually Transmitted Diseases in Ireland is producing a guidance document on the management
of STIs for healthcare professionals, which will provide more detailed information on their management.22
Chlamydia Trachomatis
Chlamydia trachomatis (C. trachomatis) genital infection is the most common curable, bacterial STI worldwide.14,23-25 Irish
figures, similar to other countries, report an overall prevalence of C. trachomatis in up to 5% of asymptomatic women
and a higher prevalence (11%) in those aged < 25 years.14,15,25,26 The clinical manifestations, diagnosis and treatment
of uncomplicated infection are summarised in Table 3. There has been an increase in the number of reported cases of
chlamydia in Ireland in recent years;23 risk factors for infection include age < 25 years, new sexual partner or > one
sexual partner in the last year, prior chlamydial infection and lack of consistent use of condoms.23,27,28 Chlamydia
is a major public health problem, which is frequently asymptomatic in men (50%) and women (70%);2,24,27 two thirds of
sexual partners of chlamydia-positive individuals are also chlamydia positive.27 C. trachomatis is associated with pelvic
inflammatory disease (PID) in up to 40% of infected untreated women, which can lead to ectopic pregnancy and tubal
factor infertility.23,24,27 The risk of developing PID increases with each recurrence of infection.27 Other complications
include neonatal transmission (neonatal conjunctivitis, pneumonia), epididymo-orchitis, and sexually acquired arthritis
(more common in men);14,27 it also facilitates the transmission of HIV in both men and women.23,24
Chlamydia screening programmes are in place in some countries, however evidence to support their effectiveness has
been questioned.24,29,30 Results of a recent Irish study did not support the establishment of an opportunistic screening
programme in Ireland.24,31 A test of cure is not routinely recommended but should be performed in pregnancy or if
non-compliance or re-exposure is suspected.27
ano-Genital warts
Genital warts are caused by the human papilloma virus (HPV) of which there are > 100 subtypes.2,20,32,33 The majority
of HPV infections are asymptomatic or subclinical.20,33,34 The clinical manifestations, diagnosis and treatment of
uncomplicated infection are summarised in Table 3. Studies suggest that up to 2% of the population up to 49 years have
had genital warts.35 Most ano-genital warts are caused by non-oncogenic HPV types 6 and 11 (90%),20,34,35 however
some lesions may contain oncogenic types associated with genital tract dysplasia and cancers (e.g. types 16 and 18).20,33,36
Those at risk of genital warts include young patients (highest incidence in 20-29 years), MSM and patients with
HIV.21,34,35 Consistent use of condoms decreases the risk of genital warts by 70%.33-35 Recent evidence suggests that
patients with genital warts have a long-term increased risk of anogenital cancers and head and neck cancers.37
Treatment of genital warts is encouraged as they are highly infectious,20 however a minority of cases resolve without
treatment.35 All treatments have significant failure and relapse rates and may involve discomfort and local skin reactions.
Podophyllotoxin and imiquimod are contra-indicated in pregnancy or lactation.38-40 Imiquimod is not recommended for
urethral, intra-vaginal, cervical, rectal or intra-anal warts and/or in tissues with open wounds.40 Local skin reactions
are common; imiquimod should be used with caution in patients with autoimmune conditions and in un-circumcised
men with foreskin associated warts.40 The impact of the introduction of the HPV vaccination for adolescent girls on the
incidence of ano-genital warts, cervical cancer, other lower ano-genital tract cancers and other HPV associated cancers
is awaited.
genital Herpes Simplex
Genital herpes is equally likely to be caused by herpes simplex type 1 (HSV-1, the usual cause of oro-labial herpes) or
herpes simplex virus type 2 (HSV-2, historically associated with sexual transmission).21,32,41 The majority of infections
are acquired subclinically.32,41 Those at increased risk of infection include younger patients, MSM and patients with
HIV.21 HSV is the most common STI in HIV patients.41 Following primary infection, the virus becomes latent in local
sensory ganglia, periodically reactivating to cause symptomatic/asymptomatic lesions and infectious viral shedding.41
Genital infection with HSV-1 has a milder natural history than infection with HSV-2 and is associated with less frequent
symptomatic recurrences and asymptomatic shedding.21,41 Condoms may be partially effective in preventing acquisition
of HSV, especially in preventing transmission from infected males to their female sex partners.41
The clinical manifestations, diagnosis and treatment of uncomplicated infection are summarised in Table 3. Many
patients with symptomatic HSV may not have the classical lesions as described and serology may be helpful in
situations including recurrent genital disease of unknown cause and investigating asymptomatic partners of patients
with genital herpes, including pregnant women.41 Complications of HSV include autonomic neuropathy (resulting in
urinary retention), autoinoculation to fingers and adjacent skin and aseptic meningitis. Recurrent HSV tends to be mild
and self-limiting and management is on an individual basis.19,41 The patient may present with healing lesions and it
may be appropriate to prescribe antiviral treatment (aciclovir or valaciclovir) for the next episode.41-43 The decision to
start continuous suppressive therapy, which should be discontinued after a maximum of 12 months, needs to take into
account the frequency of attacks (> 6 attacks annually) and the costs and inconvenience of treatment.19,41
While the risk of neonatal transmission is very low, pregnant women with a history of genital herpes should inform their
obstetrician.21,41 Perinatal transmission, associated with disseminated HSV (which is rare) in the neonate, is most likely
to occur following vaginal delivery after a first episode maternal genital HSV infection in the final trimester.19,21 The risk
of neonatal transmission is much lower with recurrent HSV lesions or asymptomatic infection.
Gonorrhoea
Gonorrhoea is caused by the bacterium Neisseria gonorrhoeae, which represents 88 million of the estimated 448
million new cases of curable global STIs occurring annually.9 Although not as common as other STIs, there has been
an increase in the incidence of gonorrhoea notified in Ireland in recent years.6,44 The prevalence of gonorrhoea is low
in the general population but the risk is increased in MSM.45 The clinical manifestations, diagnosis and treatment of
uncomplicated infection are summarised in Table 3. Frequently the infection is asymptomatic; asymptomatic carriers
are more likely to transmit the disease than people with overt infections.9 Untreated or inadequately treated gonorrhoea
results in complications including PID, epididymo-orchitis, prostatitis, arthritis, infertility and conjunctivitis.32,46
Patients with genital gonorrhoea are frequently co-infected with C. trachomatis (35% men and 41% women).32,46
Gonorrhoea is also known to facilitate the transmission of HIV infection.45 Currently of concern is the resistance of N.
gonorrhoeae to third generation cephalosporins; emerging resistance have been reported in countries including the
US, Australia, Norway and the UK.9,11,13 Referral to a specialist STI service should be considered for patients diagnosed
with gonorrhoea and is recommended for patients with penicillin allergy for appropriate treatment, testing for other STIs
and partner notification.22 A test of cure is recommended in all cases.
Syphilis
Syphilis is caused by the spirochete bacterium Treponema pallidum.14 It is a complicated infection and patients
diagnosed with syphilis should be referred to a specialist service for management.14,19 Although less common than
other STIs, similar to other developed countries, an increase of syphilis has been noted in recent years in Ireland.47-50 The
highest rates of syphilis occur in MSM;47,48,50,51 an additional risk factor is HIV infection.51 Syphilis however may also
occur in heterosexual men and in women.50 Syphilis has an incubation period of up to 90 days and is usually transmitted
during sexual contact, however transmission may occur during pregnancy and via infected blood products.52
The clinical manifestations, diagnosis and treatment of syphilis are summarised in Table 3. Syphilis can be classified
into early (primary, secondary and early latent <2 years of infection) and late (late latent >2 years of infection and
tertiary).52 Syphilis is known as “the great pretender”; it can mimic many inflammatory conditions including uveitis.53
Syphilis (+/- HIV seroconversion) should be considered in MSM presenting with a rash and in all patients presenting
with a genital ulcer.20 It is important to be aware of the signs and symptoms associated with syphilis;54 if left untreated,
it can lead to serious sequelae including cardiovascular syphilis and neurosyphilis50 and during pregnancy, to conditions
including polyhydramnios, miscarriage, pre-term labour and stillbirth.52 The immune response to syphilis involves
production of antibodies to a broad range of antigens including specific [e.g. T. pallidum enzyme immunoassay (EIA)
for immunoglobulin (Ig) G or IgM, T. pallidum haemagglutination test (TPHA) and T. pallidum particle agglutination
assay (TPPA)] and non-specific [e.g. rapid plasma regzain test (RPR)] treponemal antibodies.52,55 The first response to
infection is the production of specific treponemal IgM (detected towards the end of the second week of infection) and
IgG which appear by about 4 weeks.55 Interpretation of positive serology for syphilis requires specialist advice/
referral and a detailed history from the patient (including symptoms, treatment and previous test results).20,22
Positive tests should always be repeated on a second specimen to confirm the results,52,55 while serology should be
repeated a few weeks following a negative test if there is a high clinical suspicion of syphilis.19
Trichomoniasis
Trichomonos vaginalis is a flagellated protozoan which is found in the vagina, urethra and paraurethral glands in women
(may be carried for months or years)19 and usually in the urethra in men.56 In adults transmission is almost exclusively
sexually transmitted.56 There is evidence that trichomonos infection may enhance HIV transmission and there is concern
that it may be associated with pregnancy complications.56,57 A test of cure is recommended in all cases.22
Table 3: Clinical manifestations, testing and treatment of the common STIs
STI
***Contact tracing is an important aspect in the management of STIs***
Clinical manifestations
Diagnosis
Chlamydia (14,27,28,58) Females – (70% asymptomatic) post-coital (PCB) or
(Chlamydia
intermenstrual bleeding (IMB), lower abdominal pain,
trachomatis)
purulent vaginal discharge, mucopurulent cervicitis +/contact bleeding, dysuria.
Males – (50% asymptomatic) urethral discharge,
dysuria.
Rectal: infections usually asymptomatic but may cause
anal discharge and anorectal discomfort. Pharynx:
infections are asymptomatic and uncommon.
Genital warts
Single or multiple warts in areas including the vulva,
(20,33,38-40)
urethra, shaft of penis or scrotum, cervix, vagina, and
Human papilloma perianal area.
virus
Warts on the moist non-hair bearing skin tend to be
soft and non-keratinised and those on the dry hairy
skin firm and keratinised.
NAAT ** of first void urine
in men and women (patients
should hold urine for at least
one hour); a cervical swab or
patient-taken vulvo-vaginal
swab in women can also be
used.
Rectal +/- pharyngeal swabs
if indicated.
Visual examination in most
cases.
Biopsy may be required
for atypical or pigmented
lesions to exclude neoplastic
lesion especially in patients
with HIV.
Genital herpes
simplex
Swab from base of ulcer
– for NAAT (preferred) or
viral culture.
Primary infection – (frequently asymptomatic),
febrile illness 5-7 days, tingling/neuropathic pain in
(41,42,43,59)
genital area, extensive bilateral crops of genital blisters,
Herpes simplex virus ulcers or fissures, lymphadenitis.
type 1 and 2
Recurrent infection – usually self-limiting, unilateral
ulcers (may be small and resemble non-specific
erythema, erosions or fissures).
Gonorrhoea
Females – (50% asymptomatic), ↑ vaginal discharge,
(14,45,46,60,61)
lower abdominal pain/tenderness, dysuria, rarely IMB
(Neisseria
or PCB, mucopurulent cervicitis +/- contact bleeding.
gonorrhoeae)
Males – (95% symptomatic), urethral discharge
+/- dysuria within 2-5 days of exposure, mucopurulent
discharge commonly, rarely epididymal tenderness or
balanitis.
Rectal infection (anal discharge 12%) and pharyngeal
infection usually asymptomatic.
Syphilis
NAAT of endocervical,
vaginal and urethral swabs
(men) and urine (men
and women), rectal and
pharyngeal swabs when
indicated.
Culture and sensitivity if
possible recommended for
positive NAATs prior to
treatment.
Diagnosis can be made by
dark ground microscopy of
lesions (only in specialist
centres).
Treatment*
Azithromycin 1 gram PO stat or doxycycline 100mg PO BD
for 7 days (contraindicated in pregnancy). (Test of cure not
routinely required)
Consider referral for specialist advice in:
Pregnancy*: amoxicillin 500mg po tds x 7 days,
erythromycin 500mg po bd x 14 days or azithromycin 1 gram
PO stat.
(Test of cure recommended)
Podophyllotoxin paint/cream - apply twice daily 3 times
weekly for 4-5 weeks.
Imiquimod cream - apply 3 times per week (remove after 6-10
hours) for a maximum of 16 weeks.
Cryotherapy applied weekly until resolution.
Removal of warts under local anaesthetic – possible for
pedunculated warts and small keratinised warts at accessible
sites.
Electrosurgery or laser treatment may be required for some lesions.
Primary infection oral antiviral drugs (aciclovir, valaciclovir
and famciclovir) within 5 days of the start of the episode and
while new lesions are forming; saline baths, analgesia (+/topical lidocaine) prior to micturition. Hospitalisation may
be required for complications including urinary retention and
meningism.
Recurrent infection – see text.
Consider referral for specialist advice
Ceftriaxone 500mg IM stat plus azithromycin 1 gram po stat.
(Test of cure recommended)
Refer for specialist advice in:
Penicillin/cephalosporin allergy – treatment includes high
dose azithromycin as a single dose or ciprofloxacin (pending
sensitivity)
(Test of cure recommended)
Primary [~3weeks (1-90 days)] Painless chancre at
Refer for specialist advice
the site of inoculation.
Treatment involves multidisciplinary specialist management.
(Treponema
Secondary [~6weeks (2-12 weeks)] includes rash
Treatment decision should be made by a specialist in STI; the
pallidum)
(incl. extremities), mucous patches, condyloma
preferred treatment includes parenteral penicillin
lata, alopecia, systemic symptoms, diffuse
lymphadenopathy, neurological abnormalities.
Screen with serology
Latent - asymptomatic, positive serology; early - <2 e.g. T. pallidum specific
years, relapse likely; late >2 years, relapse improbable. EIA# Positive results to be
followed up with a different
Tertiary – [up to 30 years after exposure] spread
treponemal test.
of infection to other organs includes: neurosyphilis,
cardiovascular syphilis and gummatous syphilis.
Females – (50% asymptomatic) vaginal frothy
Trichomoniasis
High vaginal swab (females) Metronidazole 2g orally in a single dose or metronidazole
(19,56,62)
discharge, vulval soreness, dysuria, vulvitis, vaginitis, ## and urethral swab for
400mg BD for 5-7 days.
(Trichomonos
males for direct microscopy, (Test of cure recommended)
“strawberry cervix” (2%).
vaginalis)
culture and sensitivity. First
Males - (50% asymptomatic), urethral discharge
void urine (males) – culture.
+/- dysuria.
* - prescribers should refer to the Summary of Products Characteristics for full prescribing information; note that not all medicinal products are authorised for
the indication, ** - nucleic acid amplification technique, # - enzyme immunoassay, ## - cervical cytology has high false positive (30%), need confirmation
with culture from high vaginal swab
(14,52,55)
SUMMARY
It is important to consider the sexual health of all patients and the possibility of a patient having a STI, many of which are asymptomatic.
Testing for STIs is recommended for symptomatic patients and asymptomatic patients who are at risk of a STI. Patients frequently
have >1 STI present; the diagnosis of a STI should prompt a search for others that may be asymptomatic. A screen for STIs should
include testing for chlamydia, gonorrhoea, syphilis, HIV and hepatitis B. Some patients with STIs (in particular syphilis) should be
referred to a specialist setting. Partner notification is an important aspect of STI management. Medical practitioners are required to
notify STIs to the Medical Officer of Health/Director of Public Health. Management should include preventive education including
the importance of the use of condoms to prevent STIs and counselling as indicated. Patient information leaflets on STIs are available
from the Health Protection Surveillance Centre (available on www.hpsc.ie).
FOR PERSONAL USE ONLY. NOT TO BE REPRODUCED WITHOUT PERMISSION OF THE EDITOR
List of references available on request. Date of preparation: July 2012
Every effort has been made to ensure that this information is correct and is prepared from the best available resources at our disposal at the time of issue.
Prescribers are recommended to refer to the individual Summary of Product Characteristics (SmPC) for specific information on a drug.
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2012
39. SmPC Warticon® cream (podophyllotoxin) downloaded form www.medicines.ie on the 13th
July 2012
40. SmPC Aldara® (imiquimod) downloaded form www.medicines.ie on the 13th July 2012
41. British Association for Sexual Health – Clinical Effectiveness Group, 2007 National
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42. SmPC Zovirax® (acyclovir) downloaded form www.medicines.ie on the 12th July 2012
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58. SmPC Zithromax® (azithromycin) downloaded form www.medicines.ie on the 11th July
2012
59. SmPC Famvir® (famciclovir) downloaded form www.medicines.ie on the 12th July 2012
60. SmPC Rocephin® (ceftriaxone) downloaded form www.medicines.ie on the 11th July 2012
61. SmPC Ciproxin® (ciprofloxacin) downloaded form www.medicines.ie on the 16th July 2012
62. SmPC for Flagyl® (metronidazole) downloaded form www.medicines.ie on the 6th July
2012