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.
- 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 the different patterns of disease, with types D-K responsible for genitourinary infection.
It 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. Sequelae can, however, include pelvic inflammatory disease (PID), ectopic pregnancy, tubal infertility in women and proctitis, epididymitis and epididymo-orchitis in men.
- 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.
- The World Health Organization (WHO) estimates that annually 131 million new cases occur worldwide every year, the majority of which remain asymptomatic.
- In 2015, there were approximately 200,288 new diagnoses of chlamydia made in England. 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.
- 75% of cases occur in those aged under 25 - infection rates are estimated to be 1.5-10% in young people aged between 15 and 24 years.
- 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.
- Genetic predisposition.
Clinical Editor's Comments (October 2017)
Dr Hayley Willacy has recently read a small, but well powered study published online that suggests the presence of specific types of vaginal bacteria may be associated with an increased risk for chlamydia infection. The study involved 122 healthy women aged between 16 and 29 years attending an STI outpatient clinic in The Netherlands. Vaginal swab samples were collected at their first visit when all women were still free of infection. These swabs were used to unravel the structure and composition of the vaginal microbiota. One year later, these women got tested for chlamydia again - 61 tested positive. The researchers found that having a microbiota dominated by a particular strain of Lactobacillus (Lactobacillus iners) was associated with an increased risk for chlamydia infection.
In most cases the infection is asymptomatic and is often only detected during screening or investigation of other genitourinary illness.
If women are symptomatic they may describe:
- Vaginal discharge.
- Dysuria (always consider chlamydia as a cause of sterile pyuria).
- Vague lower abdominal pain.
- Intermenstrual or postcoital bleeding.
- Deep dyspareunia.
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. 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 Curtis syndrome) is a presenting feature.
- There is proctitis with mucopurulent discharge which may be due to rectal chlamydia following anal intercourse. (Rectal chlamydia is also usually asymptomatic, however.)
- There is pharyngeal infection (although this is uncommon and usually asymptomatic).
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.
Men may have:
- Epididymal tenderness.
- Mucoid or mucopurulent discharge.
- Perineal fullness due to prostatitis.
- Gonorrhoea (although co-infection is relatively common).
- Other causes of prostatitis/PID/epididymo-orchitis.
- Trichomonas vaginalis infection.
- Urinary tract infection.
- Bacterial vaginosis.
- Urethral/vaginal foreign body.
- Periurethral abscess.
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. 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.
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. Testing should be offered opportunistically in England to those who fall into this category when they visit their GP.
- 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.
In other nations where there is not a national screening programme, advice about who to screen is very similar. Scottish Intercollegiate Guideline Network (SIGN) guidelines include most of the categories above but, in the absence of a national screening programme, advise targeting of chlamydia testing on the high-risk groups, ie women between the ages of 15-19, followed by women between the ages of 20-24, and all men under the age of 25.
Screening via primary care is usually seen as acceptable. Young people prefer:
- 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.
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. 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.
The first-line recommended regimen for uncomplicated chlamydial infection is:
- Doxycycline 100 mg twice-daily for seven days (contra-indicated in pregnancy); OR
- A single dose of 1 g of azithromycin.
If these are 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.
In pregnancy (or risk of pregnancy) or breast-feeding:
- Azithromycin 1 g stat. (The British National Formulary (BNF) cautions that this should only be used if there are no alternatives but studies suggest it is safe and the British Association for Sexual Health and HIV (BASHH) and the WHO recommend its use in pregnancy.)
- Erythromycin 500 mg four times daily for seven days or twice-daily for fourteen days (nausea can result in compliance 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-compliant 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.
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 complying with treatment.
- Antibiotic side-effects and interactions.
- Avoidance of sexual intercourse (genital, oral and anal sex) even with a condom for a week after single-dose therapy or until finishing a longer regimen. The patient should not resume sex with their 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 re-infection.
- It is important to test for other STIs, including human immunodeficiency virus (HIV) and hepatitis B.
- Advice on safer sexual practices, contraception and condom use.
Reinforce with clear written information.
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. Azithromycin is now available without a prescription over-the-counter from pharmacies, 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 separate Sexually Transmitted Infections article.
Child safeguarding issues
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.
Where this is the case, seek expert paediatric advice and follow local child protection procedures.
Consider seeking expert advice by referral to a GUM clinic in the following situations:
- 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).
- PID (urgent referral in acute PID).
- 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 should be routine:
- To follow up partner notification.
- To reinforce health education messages.
- To check compliance.
- 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.
- Untreated chlamydia will either persist or spontaneously resolve. One study reported a spontaneous resolution rate of 22%. Other studies suggest up to 50% of untreated infections may resolve within a year. 95% have cleared within four years. 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. 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.
- 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 re-infection.
- 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.
- Infertility - female and possibly male.
- 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.
General preventative approaches:
- Promotion of safer sexual behaviour.
- Encouragement of early healthcare-seeking behaviour.
- Primary care involvement in prevention and sexual healthcare.
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 (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 2015, the percentage of young people tested for chlamydia ranged from 19% to 27% (highest percentage in London). The percentage testing positive ranged from 7.4% to 9.6%. In 2015 there was an overall 8% decline in the number of tests and a 7% decline in the number of diagnoses from all service settings compared to 2014
The Department of Health Public Health Outcomes Framework 2013-2016 included an indicator on the diagnosis rate for chlamydia in 15-24 year-olds. Public Health England recommends that local areas should be working towards achieving a diagnosis rate of at least 2,300 per 100,000.
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. However, a UK study concluded that the screening programme was cost-effective in terms of preventing PID. A review of randomised trials further supported the effectiveness of opportunistic screening.
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[25, 26].
Further reading and references
Wang Y, Cutcliffe LT, Skilton RJ, et al; Transformation of a plasmid-free, genital tract isolate of Chlamydia trachomatis with a plasmid vector carrying a deletion in CDS6 revealed that this gene regulates inclusion phenotype. Pathog Dis. 2013 Mar67(2):100-3. doi: 10.1111/2049-632X.12024. Epub 2013 Feb 13.
Sheringham J, Baraitser P, Simms I, et al; Chlamydia screening in England: a qualitative study of the narrative behind the policy. BMC Public Health. 2012 Apr 3012:317.
BASHH Statement on Partner Notification for Sexually Transmissible Infections (STIs); The British Association for Sexual Health and HIV, July 2012
Ricketts EJ, Francischetto EO, Wallace LM, et al; Tools to overcome potential barriers to chlamydia screening in general practice: Qualitative evaluation of the implementation of a complex intervention. BMC Fam Pract. 2016 Mar 2217:33. doi: 10.1186/s12875-016-0430-2.
Chlamydia - uncomplicated genital; NICE CKS, June 2016 (UK access)
Sexually Transmitted Infections in Primary Care; Royal College of General Practitioners and British Association for Sexual Health and HIV (Apr 2013)
Gobin M, Verlander N, Maurici C, et al; Do sexual health campaigns work? An outcome evaluation of a media campaign to increase chlamydia testing among young people aged 15--24 in England. BMC Public Health. 2013 May 1713(1):484.
Sexually Transmitted Infections (STIs); World Health Organization (WHO) Fact Sheet. December 2015
Sexually transmitted infections and chlamydia screening in England 2015 - Infection Report; Public Health England, July 2016
Malogajski J, Brankovic I, Verweij SP, et al; Translational Potential into Health Care of Basic Genomic and Genetic Findings for Human Immunodeficiency Virus, Chlamydia trachomatis, and Human Papilloma Virus. Biomed Res Int. 20132013:892106. doi: 10.1155/2013/892106. Epub 2013 May 23.
van Houdt R, Ma B, Bruisten SM, et al; Lactobacillus iners-dominated vaginal microbiota is associated with increased susceptibility to Chlamydia trachomatis infection in Dutch women: a case-control study. Sex Transm Infect. 2017 Sep 25. pii: sextrans-2017-053133. doi: 10.1136/sextrans-2017-053133.
Chan PA, Robinette A, Montgomery M, et al; Extragenital Infections Caused by Chlamydia trachomatis and Neisseria gonorrhoeae: A Review of the Literature. Infect Dis Obstet Gynecol. 20162016:5758387. doi: 10.1155/2016/5758387. Epub 2016 Jun 5.
Nwokolo NC, Dragovic B, Patel S, et al; 2015 UK national guideline for the management of infection with Chlamydia trachomatis. Int J STD AIDS. 2016 Mar27(4):251-67. doi: 10.1177/0956462415615443. Epub 2015 Nov 4.
Schoeman SA, Stewart CM, Booth RA, et al; Assessment of best single sample for finding chlamydia in women with and without symptoms: a diagnostic test study. BMJ. 2012 Dec 12345:e8013. doi: 10.1136/bmj.e8013.
Management of genital Chlamydia trachomatis infection; Scottish Intercollegiate Guidelines Network - SIGN (March 2009)
National Chlamydia Screening Programme; Public Health England
Intrauterine Contraception; Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit (2015)
Kalwij S, Macintosh M, Baraitser P; Screening and treatment of Chlamydia trachomatis infections. BMJ. 2010 Apr 21340:c1915. doi: 10.1136/bmj.c1915.
Bell G, Potterat J; Partner notification for sexually transmitted infections in the modern world: a practitioner perspective on challenges and opportunities. Sex Transm Infect. 2011 Dec87 Suppl 2:ii34-6. doi: 10.1136/sextrans-2011-050229.
When to suspect child maltreatment; NICE Clinical Guideline (July 2009)
Geisler WM, Lensing SY, Press CG, et al; Spontaneous Resolution of Genital Chlamydia trachomatis Infection in Women and Protection from Reinfection. J Infect Dis. 2013 Jun207(12):1850-6. doi: 10.1093/infdis/jit094. Epub 2013 Mar 7.
Kavanagh K, Wallace LA, Robertson C, et al; Estimation of the risk of tubal factor infertility associated with genital chlamydial infection in women: a statistical modelling study. Int J Epidemiol. 2013 Apr42(2):493-503. doi: 10.1093/ije/dyt011. Epub 2013 Mar 14.
Gotz HM, van den Broek IV, Hoebe CJ, et al; High yield of reinfections by home-based automatic rescreening of Chlamydia positives in a large-scale register-based screening programme and determinants of repeat infections. Sex Transm Infect. 2013 Feb89(1):63-9. doi: 10.1136/sextrans-2011-050455. Epub 2012 Jun 23.
Lee YS, Lee KS; Chlamydia and male lower urinary tract diseases. Korean J Urol. 2013 Feb54(2):73-7. doi: 10.4111/kju.2013.54.2.73. Epub 2013 Feb 18.
Oakeshott P, Kerry S, Aghaizu A, et al; Randomised controlled trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (prevention of pelvic infection) trial. BMJ. 2010 Apr 8340:c1642. doi: 10.1136/bmj.c1642.
Aghaizu A, Adams EJ, Turner K, et al; What is the cost of pelvic inflammatory disease and how much could be prevented by screening for chlamydia trachomatis? Cost analysis of the Prevention of Pelvic Infection (POPI) trial. Sex Transm Infect. 2011 Jun87(4):312-7. doi: 10.1136/sti.2010.048694. Epub 2011 Mar 28.
Gottlieb SL, Xu F, Brunham RC; Screening and treating Chlamydia trachomatis genital infection to prevent pelvic inflammatory disease: interpretation of findings from randomized controlled trials. Sex Transm Dis. 2013 Feb40(2):97-102. doi: 10.1097/OLQ.0b013e31827bd637.
Brunham RC, Rappuoli R; Chlamydia trachomatis control requires a vaccine. Vaccine. 2013 Apr 831(15):1892-7. doi: 10.1016/j.vaccine.2013.01.024. Epub 2013 Jan 29.
Rey-Ladino J, Ross AG, Cripps AW; Immunity, immunopathology, and human vaccine development against sexually transmitted Chlamydia trachomatis. Hum Vaccin Immunother. 201410(9):2664-73. doi: 10.4161/hv.29683.
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