Chlamydial Genital Infection

Chlamydiae are small, obligate-intracellular Gram-negative bacteria that infect human columnar and transitional epithelium. Chlamydia trachomatis is responsible for:

• Ocular infection (trachoma)
• Genitourinary infections
• Lymphogranuloma venereum (a rare, sexually transmitted tropical infection causing genital ulcers and inguinal lymphadenopathy)

Different serological variants of C. trachomatis cause the different patterns of disease with types D–K responsible for genitourinary infection.
It is the commonest treatable sexually transmitted infection in the UK¹ and the commonest preventable cause of infertility worldwide.² It is asymptomatic in ~50% of men and ~80% of women.³ The cost of investigating and treating chlamydia and its complications in the UK is estimated at over £100 million per annum.

Prevalence

Prevalence is dependent on the age and setting of the population in question:

• Overall population prevalence as estimated by postal testing survey is 2.8% in men and 3.6% in women.⁴
• In UK GP surgeries:⁵
  • <20 yrs: 8.1%
  • 20–24 yrs: 5.2%
  • 25–29 yrs: 2.6%
  • >30 yrs: 1.4%
• In genitourinary medicine clinics prevalence is as high as 17% in under-20-year-olds.
• The under-20s have a prevalence of around 12% in antenatal and termination of pregnancy clinics.⁴

Risk factors^3,6

Include:

• Age <25 (highest prevalence in the 16-19 year old range)
• New sexual partner in the last year (note, this is more important than the number of sexual partners)
• Non-barrier contraception
• Infection with another STI
• Poor socioeconomic status

The most consistent risk factor for chlamydial genital infection is young age. Why are young women more susceptible to infection? Possible reasons include:⁷

• Physical development factors
• Partial immunity has developed in older women
• Different sexual behaviour
• Less reliable condom use
• More difficulty with sexual communication
• Less appreciation of risk

Symptoms

In most cases the infection is asymptomatic and is often only detected during screening or investigation of other genitourinary illness.

Female

If women are symptomatic they may describe:

• Vaginal discharge
• Dysuria (always consider chlamydia as a cause of sterile pyuria)
• Vague lower abdominal pain
• Fever
• Intermenstrual or postcoital bleeding
• Dyspareunia

Male

Men tend to suffer either classical urethritis with dysuria and urethral discharge or epididymo-orchitis presenting as unilateral testicular pain ± swelling. Fever may also be a presenting feature in men.

In both sexes, consider chlamydial infection when:

• Young adults present with a reactive arthritis. Reiter's syndrome is a triad of urethritis, arthritis and conjunctivitis that can be triggered by chlamydial infection (amongst other pathogens), usually in conjunction with HLA B27.
• Upper abdominal pain due to perihepatitis (the Fitz-Hugh-Curtis syndrome) is a presenting feature.
• Proctitis with mucopurulent discharge which may be due to rectal chlamydia following anal intercourse.
• Pharyngeal infection (although this is uncommon and usually asymptomatic with chlamydia)

Signs

Female

In women, signs can include:

• A friable, inflamed cervix, sometimes with a follicular or 'cobblestone' appearance, with contact bleeding
• Mucopurulent endocervical discharge
• Abdominal tenderness
• Pelvic adnexal tenderness on bimanual palpation
• Cervical excitation

Sometimes, chlamydial infection in women is suggested by inflammatory changes in their cervical cytology report and this may require follow-up.

Male

Men may have:

• Epididymal tenderness
• Mucoid or mucopurulent discharge
• Perineal fullness due to prostatitis

• Gonorrhoea (although co-infection is relatively common⁸)
• Other causes of prostatitis/pelvic inflammatory disease/epididymo-orchitis
• Urethral/vaginal foreign body
• Periurethral abscess
• Ureaplasma urealyticum infection
• Mycoplasma genitalium/hominis infection
• Trichomonas vaginalis infection
• Endometriosis
• Reiter's syndrome
• Urinary tract infection
• Bacterial vaginosis

There are now a number of different techniques for detecting chlamydial infection:

• Cell culture
• Antigen detection or enzyme immunoassays (EIAs)
• Nucleic acid amplification tests (NAATs)

NAATs have largely superseded other methods due to higher sensitivity (in general, NAATs have a sensitivity of 90-95%, increased by increasing the number of patient sites sampled or the number of different NAATs used to test a sample) and the fact that testing can also be done on urine samples, reducing the need for invasive tests. Where NAATs are not available, it may be prudent to discuss with the patient the lower sensitivity of EIA tests (usually between 40-70%) and the risk of a false negative result.

• Follow local protocols for taking, storing and transporting swabs.
• In women undergoing a vaginal examination, an endocervical swab is preferred. Clean the cervix and rotate the swab 360 degrees inside the os.
• In those who are not undergoing vaginal examination, a first-void urine sample (having held urine for at least 1-2 hours previously) or self-administered vaginal swab may be used. Men should provide urine samples as this test has the same sensitivity as a urethral swab, which is painful and invasive.

Who should we be testing?

Within general practice, our exact mandate will depend on local PCT policy as regards chlamydia screening but will include:³

• Those who are symptomatic
• Infants with ophthalmia neonatorum or neonatal pneumonitis and their parents
• Opportunistic screening

Following a positive result

In some instances, primary care doctors may choose to refer to GUM (for counselling or contact tracing by appropriately trained individuals or for fuller STI screening). In other situations, these may be available as a locally enhanced service within the community. There is evidence that trained practice nurses doing partner notification and telephone follow-ups are as effective as trained health advisers in a GUM clinic and have a comparable cost.¹³

Drug treatment¹²

Current recommended regimens are:

• Doxycycline 100 mg twice daily for 7 days
• Single dose of 1 g of azithromycin (improves compliance)

If these are contraindicated, alternative regimens include:

• Ofloxacin 200 mg twice daily or 400 mg once daily for 7 days
• Erythromycin 500 mg twice daily for 10-14 days

In pregnant and breastfeeding women:

• Erythromycin 500 mg four times daily for 7 days or twice daily for 14 days
• Amoxicillin 500 mg three times daily for 7 days
• Azithromycin 1 g stat (but the BNF cautions that this should only be used if there are no alternatives)

Longer courses of antibiotics are needed for cases of salpingitis or upper genital tract infection in men.

A test of cure is not routine unless the patient is pregnant, has been noncompliant or been re-exposed. Wait for 5 weeks post end of treatment (or 6 weeks with azithromycin).

General advice

Provide clear explanation of the condition and its long term implications for the patient and their partner(s). Key points include:

• Chlamydia is primarily sexually transmitted.
• Infection is very often asymptomatic and may have persisted for many months or even years.
• No diagnostic test is 100% sensitive.
• Potential complications of not treating chlamydia.
• The importance of investigating and treating sexual partners. Agree on method of partner notification.
• The importance of complying with treatment.
• Antibiotic side-effects and interactions with hormonal contraception.
• The need to abstain from sexual intercourse (including oral sex) even with a condom for a week after single-dose therapy or until finishing a longer regimen.
• Do not resume sex with your partner(s) until they too have completed treatment (or for a week following stat dose of azithromycin) or received negative test results, otherwise there is a high risk of reinfection.
• It is important to test for other sexually transmitted infections including Human Immunodeficiency Virus (HIV) and Hepatitis B.
• Advice on safer sexual practices and condom use.

Reinforce with clear written information.

Sexual partners

In the UK, the 'look-back' period for partner tracing is somewhat arbitrary but is taken as:

• 4 weeks where an individual is symptomatic
• 6 months or to the last previous sexual partner (whichever is longest) in asymptomatic individuals

Those identified should be informed of their risk, offered treatment, contact tracing and STI testing. Where partners decline 'epidemiological treatment', they should be advised to abstain from sex until they have a negative test result.

Follow-up

Follow-up should be routine:

• To follow up partner notification
• To reinforce health education messages
• To check compliance
• To retreat where necessary

Evidence suggests that telephone follow-up is at least as good as face-to-face and more cost effective.

• Untreated chlamydia will either persist or spontaneously resolve. Factors determining which course an infection takes are not fully understood, nor the period of time over which asymptomatic infection can persist.
• About two-thirds of the sexual partners of an individual with chlamydia will also test positive for chlamydia.⁶
• Antibiotic treatment is effective in at least 95% of cases if the full course is taken. Outlook is generally good if treated early with full compliance. Long term infection is associated with a higher rate of complications, particularly infertility in women.
• Consider recurrence and repeat testing in those who remain symptomatic. A Dutch study looking at home-based screening in 15-29 year olds found that 10.4% of those who initially screened positive for chlamydia, remained positive a year later. Looking at subtypes, approximately half were new infections and half persisting infections (or re-infections with the same organism).¹⁴

• Infertility - female and possibly male¹⁵
• Urethral stricture and scarring in men
• Pelvic inflammatory disease
• Increased risk of cervical carcinoma
• Perihepatitis as part of Fitz-Hugh-Curtis syndrome
• Neonatal ophthalmic infection/pneumonia
• Reiter's syndrome

In 2001, the Government's Sexual Health Strategy recommended chlamydial screening based on evidence that a targeted screening programme could reduce chlamydia-related morbidity and complications.

There have been several large scale studies over the first part of this decade looking at the best way to implement national screening - whether to reach the target group (<25 years) opportunistically or via a register-based population strategy? The CLASS (ChLAmydia Screening Study) invited men and women in the 16 to 39 year age bracket to provide a urine specimen or self-taken vaginal swab and return by post for NAAT. It showed that whilst postal screening is feasible, uptake was much lower than might be anticipated (35%) and worse in deprived areas and ethnic minorities, raising the spectre of increasing health inequalities.⁴ Cost-effectiveness of both opportunistic¹⁷ and proactive register-based screening¹⁸ approaches has been questioned.

The current strategy is to increase awareness and to offer annual,opportunistic screening to the sexually active, under 25s and to make testing/treatment easily available via a wide variety of traditional healthcare settings (GPs, Family Planning clinics, Gynaecology out patients, GUM clinics, abortion services) and less conventional healthcare settings (community pharmacies, prison health services, young peoples' services) but also outside of healthcare settings (e.g. further and higher education, youth clubs, outreach units and postal kits for use at home).