Chlamydial genital infection

What is a 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.

• Proctitis.

• Sexually acquired reactive arthritis.

• Lymphogranuloma venereum (a rare, sexually transmitted tropical infection causing genital ulcers and inguinal lymphadenopathy).

Different serological variants of C. trachomatis cause different patterns of disease, with types D-K responsible for genitourinary infection.

Chlamydial genital infection is the most commonly diagnosed sexually transmitted infection (STI) in the UK and the most common preventable cause of infertility worldwide. It is asymptomatic in approximately 50% of men and at least 70% of women.¹ Sequelae can include pelvic inflammatory disease (PID), ectopic pregnancy, tubal infertility in women and proctitis, epididymitis and epididymo-orchitis in men.²

How common are chlamydial genital infections? (Epidemiology)

Prevalence

• Prevalence is dependent on the age and setting of the population in question. It is highest in sexually active people under the age of 25.^{1 3}

• The World Health Organization (WHO) estimates that annually 131 million new cases occur worldwide every year, the majority of which remain asymptomatic.⁴

• In 2019, there were approximately 229,411 new diagnoses of chlamydia made in England; around 60% of these diagnoses were made in those aged 15-24.¹

• This represented 46% of new STI diagnoses and a decrease of 4% from the previous year. It is thought this may have been due to a reduction in the numbers presenting for screening.The numbers presenting for screening via the National Chlamydia Screening Programme in 2020 dropped by 30% compared to 2019 and there was a proportional drop in positive tests from screening, of 31% compared to 2019.

Risk factors for chlamydial genital infections^{1 2}

These include:

• Age <25 years.

• Sexual partner positive for chlamydia (two thirds of partners of people testing positive for chlamydia will test positive).

• Two or more sexual partners in the preceding year.

• A recent change in sexual partner.

• Lack of consistent use of condoms.

• Non-barrier contraception.

• Infection with another STI.

• Poor socio-economic status.

• A 2017 study suggests that the composition of the vaginal microbiota may affect the risk of catching chlamydia - this is not something that we currently test for as part of routine care.⁵

Presentation

Symptoms of chlamydial genital infections

In most cases, the Chlamydial genital 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.

• Deep dyspareunia.

Male
Men tend to have 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 (more often males) present with a reactive arthritis. Within the various types of 'reactive arthritis' there 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 (Fitz-Hugh Curtis syndrome) is a presenting feature.

• There is proctitis with mucopurulent discharge which may be due to rectal chlamydia following anal intercourse. Rectal infection can also be asymptomatic and has been found in women who do not report having anal sex.⁶

• There is pharyngeal infection (although this is uncommon and usually asymptomatic).⁷

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.

Male
Men may have:

• Epididymal tenderness.

• Mucoid or mucopurulent discharge.

• Perineal fullness due to prostatitis.

Differential diagnosis

• Gonorrhoea (although co-infection is relatively common).

• Other causes of prostatitis/PID/epididymo-orchitis.

• Trichomonas vaginalis infection.

• Urinary tract infection.

• Bacterial vaginosis.

• Endometriosis.

• Urethral/vaginal foreign body.

• Periurethral abscess.

Investigations⁶

Samples are taken for nucleic acid amplification tests (NAATs), currently the most sensitive and specific method of testing for chlamydia.

In women, a vulvovaginal swab is now the specimen of choice and has been shown to be more sensitive than endocervical swabs.⁶ The swab is inserted about 5 cm into the vagina and rotated gently for 10-30 seconds. Less sensitive alternatives are endocervical swabs or first catch urine specimens. For the latter, advise the person they should not have passed urine for at least the previous hour, and then catch the first 20 ml of the sample for testing.

For men, the test of choice is a first catch urine specimen (taken as for women above), which is at least as sensitive as the alternative of urethral sampling and more acceptable as a test. If urethral samples are taken, the swab should be inserted 2-4 cm into the urethra and rotated once.

Who should be tested for chlamydia?¹

This is dependent on local guidelines and screening policy. In England this would normally include:

• Men or women with symptoms which could indicate infection.

• Sexual partners of people with proven or suspected chlamydia .

• All sexually active people younger than 25 years of age, annually, or more frequently if they have changed their partner, as part of the national screening programme.⁸

• People under 25 years of age who have been treated for chlamydia in the past three months.

• People who have concerns about sexual exposure. (If exposure was in the previous two weeks, test and repeat two weeks post-exposure.)

• People who have had two or more sexual partners in the past year.

• All women presenting for termination of pregnancy.

• All those presenting at a genitourinary medicine (GUM) clinic.

• Mothers of infants with chlamydial infection (eg, neonatal chlamydial conjunctivitis or pneumonia).

• Women who are about to be fitted with an intrauterine contraceptive device (IUCD) or intrauterine system (IUS) who are identified as at risk of STI.⁹

In other nations where there is not a national screening programme, advice about who to screen is very similar.

Screening via primary care is usually seen as acceptable. Young people prefer:¹⁰

• The use of the word 'test' rather than 'screen'.

• Testing to be normalised: "It's something we offer to all young people."

• Routine 'offering' of testing - rather than putting the impetus on them to ask.

• Emphasis that the test is free, painless, self-administered and, if positive, easy to treat.

Chlamydial genital infection treatment and management^{2 11}

When faced with a positive result, local policies may vary but the following is needed:

• Antibiotic treatment of the index case.

• Screening for other STIs.

• Partner notification.

This is managed between the GP and the GUM clinic and as a GP you may refer for any/all of these aspects or manage some/all within the practice, as long as management conforms to national standards. Treatment for STIs from a GUM clinic is free, which may influence choice as those who are not exempt from prescription charges will have to pay if treated by their GP.

For most, screening and partner notification are best carried out in the specialist setting of a GUM clinic, unless there is expertise within the practice, or the patient is unable or unwilling to attend a GUM clinic.Many GUM services have been shut in the last few years, which may mean that patients have to travel a longer distance, which they may be unwilling to do.¹²

Antibiotics^{1 6}

The first-line recommended regimen for uncomplicated chlamydial infection is:

• Doxycycline 100 mg twice-daily for seven days (contra-indicated in pregnancy and breastfeeding).

• If doxycycline is contra-indicated or not tolerated, consider azithromycin 1 g on the first day, followed by 500 mg once daily for two days.

If these are both contra-indicated, alternative regimens are:

• Erythromycin 500 mg twice-daily for ten to fourteen days.

• Ofloxacin 200 mg twice-daily or 400 mg once-daily for seven days (however this is contra-indicated in pregnancy, children and growing adolescents).

This guidance is a relatively recent change (2018) - previous guidance suggested either doxycycline or azithromycin (1 g stat) as the first line option. The reason for the change is two-fold:

1. An increasing number of people with chlamydia are co-infected with Mycoplasma genitalium, an infection which is difficult to test for and is increasingly resistant to macrolides.

2. Azithromycin is less effective than doxycycline in treating rectal chlamydia and studies have shown significant rates of concomitant rectal chlamydia in women, even when there is no history of anal intercourse.

Individual clinicians may need to use clinical judgment as to the likelihood of a patient completing a seven day course of antibiotics.

In pregnancy (or risk of pregnancy) or breastfeeding:

• When treating a pregnant woman, her management should ideally be discussed with other professionals involved in her care e.g. her midwife and obstetrician, and with a GUM clinic.

• Azithromycin 1g on the first day then 500 mg once daily for the next two days. (The British National Formulary (BNF) cautions that this should only be used if adequate alternatives are not available, but studies suggest it is safe and the British Association for Sexual Health and HIV (BASHH) and the WHO recommend its use in pregnancy.)¹³

• Erythromycin 500 mg four times daily for seven days or twice-daily for fourteen days (nausea can result in adherence issues).

• Amoxicillin 500 mg three times daily for seven days (penicillins can induce latency and later reactivation - discuss with a GUM consultant).

• Doxycycline and ofloxacin are contra-indicated in pregnancy.

• Women treated in pregnancy should have a test of cure three weeks later.

Repeat testing after treatment

A test of cure is not routine unless the patient is pregnant, has persistent symptoms, has been non-adherent or has been re-exposed. Where needed it should be done at least three weeks after treatment. In England, the national screening programme recommends that young people under the age of 25 who have tested positive for chlamydia should have a repeat test three months later. A second positive result may be due to:

• Poor adherence to treatment.

• Re-infection from an untreated or new partner.

• Inadequacy of treatment.

• A false positive result.

General advice for people with a chlamydial genital infection

Provide a 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 for years.

• No diagnostic test is 100% sensitive.

• Potential complications of not treating chlamydia.

• The importance of investigating and treating sexual partners. Agree on the method of partner notification.

• The importance of adhering with treatment.

• Antibiotic side-effects and interactions.

• Avoidance of sexual intercourse (genital, oral and anal sex) even with a condom for a week after finishing their antibiotics. The patient should not resume sex with their partner(s) until a week after they too have completed treatment; otherwise there is a high risk of re-infection.

• It is important to test for other STIs, including human immunodeficiency virus (HIV), syphilis and hepatitis B. Swabs used in primary care usually test for gonorrhoea at the same time as chlamydia, but if this is not the case then the patient should also be tested for gonorrhoea.

• Advice on safer sexual practices, contraception 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:

• Four weeks prior to developing symptoms where a male individual has urethral symptoms, and all contacts since developing symptoms.

• All contacts in the last six months of asymptomatic individuals and symptomatic women and men with symptoms other than urethral.

Those identified should be informed of their risk and offered treatment, contact tracing and STI testing. Where suitably trained, practice nurses or other trained healthcare professionals may be able to offer partner notification as effectively as GUM clinics. Partners can be notified by the index patient themselves (patient referral) or by health professionals (provider referral). Where partners decline 'epidemiological treatment', they should be advised to abstain from sex until they have a negative test result.

Text messaging, web-based systems, home sampling and expedited partner therapy (treatment given to the index patient to provide to the partner) are options which help to improve the effectiveness of partner notification and treatment. Referring partners to local pharmacies and prescribing after telephone consultations have also been found helpful.¹⁴ . Azithromycin is now available without a prescription after a consultation with a pharmacist, following its reclassification; it is indicated for men and women over 16 years old who are asymptomatic and have tested positive for chlamydia and for the treatment of their sexual partners, without the need for a test.

Testing for other STIs

Do not think about chlamydia in isolation to other STIs; patients who have tested positive for chlamydia should be encouraged to undergo a full STI screen, including testing for HIV and hepatitis B. This is usually undertaken in the GUM clinic. See the separate Sexually Transmitted Infections article.

Child safeguarding issues¹⁵

Sexual abuse must be considered in any child or young person with chlamydia, particularly when:

• A child is aged <13 years without clear evidence of vertical transmission during birth, or of blood contamination.

• A young person is aged 13-15 years without clear evidence of vertical transmission during birth, blood contamination, or that the STI was acquired from consensual sexual activity with another young person.

• A young person is aged 16-17 years without clear evidence of blood contamination or that the STI was acquired from consensual sexual activity. Consider also possible differences in power or mental capacity between the young person and their sexual partner (eg, incest, an adult in a position of trust, such as a teacher, sports coach, minister of religion) or the possibility of exploitation or online grooming.

Where this is the case, seek expert paediatric advice and follow local child protection procedures.

Referral

Consider seeking expert advice by referral to a GUM clinic in the following situations. This list was taken from a now withdrawn gov.uk document - it no longer appears in any national guidance but has been left here as a checklist for situations in which those in primary care may wish to seek specialist advice. The threshold for referral will vary depending on the primary care expertise in this area.

• All cases where chlamydia is confirmed where aspects of management cannot be managed according to national standards within primary care (eg, screening for other STIs, partner notification).

• Pregnancy (urgent if pelvic pain).

• Intolerance of treatment.

• Diagnostic uncertainty - eg, an equivocal test result, atypical symptoms.

• Presence of ongoing symptoms despite treatment.

• Multiple sexual partners.

• Complicated upper genital tract infection (usually referral to gynaecologist, urgently where indicated).

Follow-up

Follow-up should be routine:

• To follow up on partner notification.

• To reinforce health education messages.

• To check adherence.

• To re-treat where necessary.

• To arrange repeat testing where indicated.

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

Prognosis

• Untreated chlamydia will either persist or resolve spontaneously- up to 50% of cases will resolve within 12 months of diagnosis.¹ 95% have cleared within four years.² Factors determining which course an infection takes are not fully understood; neither is the period of time over which asymptomatic infection can persist.

• The natural history of chlamydial infection remains elusive. There is much debate as to the rates of progression to PID and infertility, with the NICE CKS page giving a figure of up to 16% developing PID, but a wide range of 1-20% for the risks of tubal infertility after PID. A Scottish study reported that for women with a current or past chlamydial infection the risk of tubal infertility was 0.9% in women aged 25-29 and 1.4% in those aged 35-39.¹⁶

• Antibiotic treatment is effective in at least 95% of cases if the full course is taken.¹¹ Outlook is generally good if treated early with full compliance.

• About two thirds of the sexual partners of an individual with chlamydia will also test positive for chlamydia, emphasising the need for contact tracing and synchronised treatment of partners to prevent re-infection.² Partners of those with chlamydia should be treated when they present for a test, before the result is back.⁶

• Consider recurrence and repeat testing in those who remain symptomatic. A Dutch study looking at home-based screening found that 8.8% of those who initially screened positive for chlamydia, remained positive six months later.¹⁷

Complications²

• PID.

• Infertility - female and possibly male.¹⁸

• Ectopic pregnancy.

• Epididymo-orchitis, urethral stricture and scarring in men.

• Perihepatitis as part of Fitz-Hugh and Curtis syndrome.

• Reactive arthritis.

Of infection during pregnancy

• Premature rupture of membranes, preterm delivery and low birth weight.

• Postpartum endometritis.

• Neonatal ophthalmic infection/pneumonia.

Chlamydial genital infection prevention

General preventative approaches:¹⁰

• Promotion of safer sexual behaviour.

• Encouragement of early healthcare-seeking behaviour.

• Primary care involvement in prevention and sexual healthcare.

Screening

In 2001, the Government's Sexual Health Strategy recommended chlamydial screening in England based on evidence that a screening programme could reduce chlamydia-related morbidity and complications. The current National Chlamydia Screening Programme's strategy is to reduce the prevalence and transmission of chlamydia by:

• Ppromoting public awareness of the disease; and

• Offering annual, opportunistic screening to sexually active men and women aged under 25; and

• Providing easy access to testing and treatment via a wide range of healthcare settings, as well as settings outside of healthcare (eg, further and higher education, youth clubs, outreach units and postal kits for use at home).

Chlamydia testing coverage, detection rate and percentage testing positive vary by area of residence within England. In 2020, the percentage of young people tested for chlamydia ranged from 10.6% to 19.3% (highest percentage in London). The percentage testing positive ranged from 7.9% to 11.2%. In 2020 there was an overall 29.6% decline in the number of tests and a 30.9% decline in the number of diagnoses from all service settings compared to 2019.

There have been many challenges to the assumptions underpinning the screening programme, including the Prevention of Pelvic Infection (POPI) trial which showed that most cases of PID occurred in women who had tested negative for chlamydia at baseline, implicating incident infection and casting doubt over the effectiveness of a single annual test for chlamydia to prevent PID.¹⁹ However, a UK study concluded that the screening programme was cost-effective in terms of preventing PID.²⁰ A review of randomised trials further supported the effectiveness of opportunistic screening.²¹

The reduction in the duration of the period between detection and treatment which results from the screening programme will, in turn, have an effect on herd immunity. The control of infection in the community would benefit from the development of an effective vaccine and there is work being carried out in this area.^{22 23}