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 most common treatable sexually transmitted infection (STI) in the UK¹ and the most common preventable cause of infertility worldwide.² It is asymptomatic in approximately 50% of men and 80% of women³ but sequelae can include pelvic inflammatory disease (PID), ectopic pregnancy, tubal infertility in women and epididymitis and epididymo-orchitis in men.

Whilst the benefit of detection and subsequent treatment for affected individuals seems clear, argument remains as to the best means to control chlamydia within a population. A national screening programme has been rolled out in England since 2003⁴ but debate remains as to its efficacy and cost-effectiveness. Important modelling assumptions, such as the true prevalence in the population, patterns of transmission and rates of progression to serious complications, are not widely agreed. In Scotland, current guidelines conclude: 'in the absence of data to support a complication rate of 10% or more in women with untreated chlamydial infection, there is no evidence that a screening programme for chlamydia is cost effective with regard to reducing morbidity' and testing of asymptomatic patients is limited to a targeted approach.⁵

Epidemiology

Prevalence

Prevalence is dependent on the age and setting of the population in question. Estimates of population prevalence are based on:

• Postal testing survey - 2.8% in men and 3.6% in women.⁶
• UK GP surgery attendances - 4-5% of women aged under 20.⁷
• Genitourinary medicine (GUM) clinic attendances - 17% in under 20 year-olds.
• Termination of pregnancy (TOP) and antenatal clinics - 12% in under 20 year-olds.⁶

The number of diagnoses has risen over the past decade but this is thought to reflect the use of more sensitive tests and increased rates of testing rather than increasing rates of disease alone.⁸

Risk factors^3,9

These include:

• Age <25 (the highest prevalence in women occurs between ages 16-19 years and in men between ages 20-24 years)
• Two or more sexual partners in the last year.
• A recent change in sexual partner.
• 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:¹⁰

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

Presentation

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.

• 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 (Fitz-Hugh and 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.

Differential diagnosis

• Gonorrhoea (although co-infection is relatively common¹¹).
• 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.

Investigations³

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).
• With reactive arthritis, paired serology may detect rising titres.

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° 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.

There is interest in the use of rapid point-of-care testing that could allow a test-and-treat in a single visit approach.¹² However, a recent review suggests that NAATs are still the most accurate and cost-effective method for diagnosing chlamydial infection and concludes that there is little evidence as yet guiding the use of rapid point-of-care methods.¹³

Management⁹

Who should we be testing?

Within general practice, our exact mandate will depend on local primary care trust (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.

• 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.

Others who are advised to undergo screening include:^15,16

• Women requesting termination of pregnancy (TOP).
• Patients undergoing intrauterine contraceptive device (IUCD) insertion, with risk factors.
• Patients with another STI including genital warts,
• Patients with new or multiple partners in the preceding year.
• Patients with a partner with a recent STI.
• Patients attending a GUM clinic.
• Parents of infants with chlamydial conjunctivitis or pneumonitis.
• Semen and egg donors.
• Patients with tubal infertility or ectopic pregnancy.

The National Institute for Health and Clinical Excellence (NICE) does not currently recommend screening during pregnancy.¹⁷

Following a positive result

Institute treatment ahead of test results in those with signs or symptoms strongly suggestive of chlamydia.¹⁸

In some instances, primary care doctors may choose to refer to a GUM clinic (for counselling or contact tracing by appropriately trained individuals or for fuller STI screening). However, about half of those referred to GUM clinics from primary care fail to attend.¹⁹ 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.²⁰

Drug treatment⁹

The treatment of chlamydia is straightforward; current recommended regimens are:

• Single dose of 1 g of azithromycin - best for compliance.
• Doxycycline 100 mg twice-daily for 7 days.

If these are contra-indicated, alternative regimens include:

• Ofloxacin 200 mg twice-daily or 400 mg once-daily for 7 days.
• Erythromycin 500 mg twice daily for 14 days, or four times daily for 7 days.
• Amoxicillin 500 mg three times daily for 7 days.

In pregnant and breast-feeding 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 British National Formulary 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 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 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 complying with treatment.
• Antibiotic side-effects and interactions.
• Avoid sexual intercourse (genital, oral and anal 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, 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:

• 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. 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.

Augmenting patient referral with patient delivered treatment, home sampling and additional information for partners improves outcomes.²¹ Patient delivered partner treatment is potentially a popular option²² and variants such as referring partners to local pharmacies or providing treatment following a telephone consultation are being piloted. Azithromycin (Clamelle®) is now available without a prescription over-the-counter from pharmacies, following its reclassification, and 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:

• Ideally, perform the full STI screen prior to giving treatment for chlamydia (as STIs may go undiagnosed following antibiotic treatment).
• Where a full STI screen is not possible in the community, do not delay treatment for chlamydia until seen at a GUM clinic, but screening for other STIs should be delayed for at least a week after the completion of antibiotic treatment.

• A child is <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 a peer.
• 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 (e.g. incest, an adult in a position of trust, such as a teacher, sports coach, minister of religion) or the possibility of exploitation.

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

Referral:¹⁶
Seek expert advice/refer to GUM where:

• Pregnancy.
• Pelvic inflammatory disease (PID) (but start treatment in advance).
• Intolerance of treatment.
• Diagnostic uncertainty, e.g. equivocal test result, atypical symptoms.
• Ongoing symptoms despite treatment.
• Difficulty with partner notification.

Urgent referral where:

• Acute, severe PID or lack of response to treatment for PID.
• Pelvic pain in pregnancy.

• 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.

Prognosis

• Untreated chlamydia will either persist or spontaneously resolve. 46% of infections clear spontaneously within a year. 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 pelvic inflammatory disease (PID) and infertility. One systematic review estimated incidence of PID as 0-30% in women with untreated chlamydia.²³ Another review estimated that 10-20% of women with PID develop tubal infertility and that women with chlamydia have 0.1-6% risk of developing tubal infertility.
• 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.
• 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 reinfection.⁹
• 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 reinfections with the same organism).²⁴

Complications

• Pelvic inflammatory disease (PID).
• Infertility - female and possibly male.²⁵
• Ectopic pregnancy.
• Urethral stricture and scarring in men.
• Perihepatitis as part of Fitz-Hugh and Curtis syndrome.
• Reiter's syndrome.

Of infection during pregnancy:

• Premature rupture of membranes, preterm delivery and low birthweight.
• Neonatal ophthalmic infection/pneumonia.

Prevention

General preventative approaches:⁸

• Promotion of safer sexual behaviour.
• Encourage 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 promoting public awareness of the disease, 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 (e.g. further and higher education, youth clubs, outreach units and postal kits for use at home). Uptake had been poor initially but has steadily risen, reaching 22% nationally in the year 2009-10.⁴ However, uptake must continue to rise to achieve cost effectiveness and an impact on prevalence.

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 pelvic inflammatory disease (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 chlamydia test to prevent PID.²⁶ A recent systematic review concluded that there was insufficient current evidence to support the effectiveness of opportunistic screening, that further trial evidence was required to evaluate the use of multiple rounds of the screening approach and fuller evaluation of the possible harms of screening was needed.²⁷ Screening is not without cost, both financial (bringing significant opportunity costs to the NHS) and to individuals with anxieties regarding, relationships, future fertility and contraceptive choices.²⁸

Document references

1. Griffiths C, Cuddigan A; Clinical management of chlamydia in general practice: a survey of reported practice. J Fam Plann Reprod Health Care. 2002 Jul;28(3):149-52. [abstract]
2. Paavonen J, Eggert-Kruse W; Chlamydia trachomatis: impact on human reproduction. Hum Reprod Update. 1999 Sep-Oct;5(5):433-47. [abstract]
3. Sexually Transmitted Infections in Primary Care, British Association for Sexual Health and HIV (2006)
4. NHS National Chlamydia Screening Programme
5. Management of Genital Chlamydia trachomatis Infection, Scottish Intercollegiate Guidelines Network (March 2009)
6. Macleod J, Salisbury C, Low N, et al; Coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and prevalence of infection in the United Kingdom general population: cross sectional study. BMJ. 2005 Apr 23;330(7497):940. Epub 2005 Apr 4. [abstract]
7. Adams EJ, Charlett A, Edmunds WJ, et al; Chlamydia trachomatis in the United Kingdom: a systematic review and analysis of prevalence studies. Sex Transm Infect. 2004 Oct;80(5):354-62. [abstract]
8. Kalwij S, Macintosh M, Baraitser P; Screening and treatment of Chlamydia trachomatis infections. BMJ. 2010 Apr 21;340:c1915. doi: 10.1136/bmj.c1915.
9. Management of Chlamydia trachomatis genital tract infection, British Association for Sexual Health and HIV (2006)
10. Navarro C, Jolly A, Nair R, et al; Risk factors for genital chlamydial infection. Can J Infect Dis. 2002 May;13(3):195-207. [abstract]
11. Das S, Sabin C, Wade A, et al; Sociodemography of genital co-infection with Neisseria gonorrhoeae and Chlamydia trachomatis in Coventry, UK. Int J STD AIDS. 2005 Apr;16(4):318-22. [abstract]
12. Nadala EC, Goh BT, Magbanua JP, et al; Performance evaluation of a new rapid urine test for chlamydia in men: BMJ. 2009 Jul 28;339:b2655. doi: 10.1136/bmj.b2655. [abstract]
13. Hislop J, Quayyum Z, Flett G, et al; Systematic review of the clinical effectiveness and cost-effectiveness of rapid Health Technol Assess. 2010 Jun;14(29):1-97, iii-iv. [abstract]
14. Salisbury C, Macleod J, Egger M, et al; Opportunistic and systematic screening for chlamydia: a study of consultations by young adults in general practice. Br J Gen Pract. 2006 Feb;56(523):99-103. [abstract]
15. Oakeshott P, Hay P, Pakianathan M; Chlamydia screening in primary care. Br J Gen Pract. 2004 Jul;54(504):491-3.
16. Diagnosis of Chlamydia. Quick Reference Guide for GPs, Health Protection Agency (2008)
17. Antenatal care: routine care for the healthy pregnant woman, NICE Clinical Guideline (March 2008)
18. Chlamydia - uncomplicated genital, Clinical Knowledge Summaries (May 2009)
19. Oakeshott P, Graham A; NICE guidance on one-to-one interventions to reduce sexually transmitted Sex Transm Infect. 2007 Apr;83(2):171-2.
20. Low N, McCarthy A, Roberts TE, et al; Partner notification of chlamydia infection in primary care: randomised controlled trial and analysis of resource use. BMJ. 2006 Jan 7;332(7532):14-9. Epub 2005 Dec 15. [abstract]
21. Trelle S, Shang A, Nartey L, et al; Improved effectiveness of partner notification for patients with sexually BMJ. 2007 Feb 17;334(7589):354. [abstract]
22. Melvin L, Cameron ST, Glasier A, et al; Preferred strategies of men and women for managing chlamydial infection. BJOG. 2009 Feb;116(3):357-65. [abstract]
23. Risser WL, Risser JM; The incidence of pelvic inflammatory disease in untreated women infected with Int J STD AIDS. 2007 Nov;18(11):727-31. [abstract]
24. Veldhuijzen IK, Van Bergen JE, Gotz HM, et al; Reinfections, persistent infections, and new infections after general population screening for Chlamydia trachomatis infection in the Netherlands. Sex Transm Dis. 2005 Oct;32(10):599-604. [abstract]
25. Gallegos G, Ramos B, Santiso R, et al; Sperm DNA fragmentation in infertile men with genitourinary infection by Chlamydia trachomatis and Mycoplasma. Fertil Steril. 2007 Oct 20;. [abstract]
26. Oakeshott P, Kerry S, Aghaizu A, et al; Randomised controlled trial of screening for Chlamydia trachomatis to prevent BMJ. 2010 Apr 8;340:c1642. doi: 10.1136/bmj.c1642. [abstract]
27. Low N, Bender N, Nartey L, et al; Effectiveness of chlamydia screening: systematic review. Int J Epidemiol. 2009 Apr;38(2):435-48. Epub 2008 Dec 5. [abstract]
28. Kangas I, Andersen B, Olesen F, et al; Psychosocial impact of Chlamydia trachomatis testing in general practice. Br J Gen Pract. 2006 Aug;56(529):587-93. [abstract]

Internet and further reading

• One to one interventions to reduce the transmission of sexually transmitted infections (STIs), NICE Public Health Guidance (February 2007); Including HIV, and to reduce the rate of under 18 conceptions, especially among vulnerable and at risk groups
• Houry DE; Chlamydia, eMedicine, Apr 2010
• Struble K et al; Chlamydial Genitourinary Infections, eMedicine, Mar 2010
• Guidelines for the management of genital chlamydia infections, Health Protection Agency

Acknowledgements