Abstract
Sexually transmitted Chlamydia trachomatis infections remain common globally and most frequently are asymptomatic. The 2025 European C. trachomatis guideline provides up-to-date guidance regarding indications for testing and treatment of C. trachomatis infections. It includes advice on urogenital and extragenital C. trachomatis testing including the use of self-collected specimens; recommendation to use only validated NAATs for diagnosis; and recommendation to treat all C. trachomatis infections with doxycycline as first line in preference to single-dose azithromycin regimens. The absence of evidence and limited value of broad screening in asymptomatic populations for C. trachomatis infections is also discussed.
Aetiology, transmission and epidemiology
Chlamydia trachomatis is a common sexually transmitted infection 1 with the majority of infections being asymptomatic (no symptoms recognised by the individual who is infected), especially in women and extragenital infections. 2
Notification rates continue to be highest among young adult heterosexual women (https://atlas.ecdc.europa.eu/public/index.aspx, https://www.ecdc.europa.eu/sites/default/files/documents/Syst-review-prevalence-stis.pdf). 3 Younger age and behavioural risk factors such as prior C. trachomatis infection, condomless sex and new or multiple partners remain the major risk factors for acquisition. 4
Transmission of C. trachomatis usually occurs via direct mucosal contact between individuals during sexual intercourse (vaginal, anal or oral sex); vertical transmission can result from vaginal delivery through an infected cervical canal. 2
Clinical features, complications and sequelae
Spontaneous clearance occurs in most untreated asymptomatic women at an estimated rate of 45–54% at 1 year of follow-up, 82% at 2 years, and 94% at 4 years.5,6 A long duration of undetected and untreated infection in women can result in ascending infection causing pelvic inflammatory disease (PID) and associated sequelae such as ectopic pregnancy, chronic pelvic pain and tubal factor infertility. 2
Urogenital infections
Symptoms and signs in women
• 70–95% asymptomatic
2
• Dysuria • Vaginal discharge • Postcoital bleeding and intermenstrual bleeding • Menorrhagia • Abdominal pain or lower abdominal pain • Mucopurulent cervicitis, with or without contact bleeding • Cervical friability • Cervical oedema • Endocervical ulcers • Urethritis
Symptoms and signs suggestive of PID
• Lower abdominal tenderness and pain – usually bilateral7–9 • Deep dyspareunia – particularly of recent onset • Abnormal vaginal bleeding – intermenstrual bleeding, post coital bleeding and menorrhagia can occur secondary to associated cervicitis and endometritis • Abnormal vaginal or cervical discharge – as a result of associated cervicitis, endometritis or bacterial vaginosis • Cervical motion tenderness on bimanual vaginal examination • Adnexal tenderness on bimanual vaginal examination – unilateral or bilateral • Fever (>38°C) – in moderate to severe PID
Complications of C. trachomatis in women (see also below)
• PID (endometritis, salpingitis, parametritis, oophoritis, tubo-ovarian abscess and/or pelvic peritonitis)
2
• Chronic pelvic pain • Tubal factor infertility • Ectopic pregnancy • Sexually acquired reactive arthritis (SARA) • Fitz-Hugh-Curtis syndrome (PID and perihepatitis)
Symptoms and signs in men
Complications in men (see also below)
• SARA
2
• Epididymo-orchitis
Rectal and pharyngeal infections
C. trachomatis infections of the rectum (non-LGV serovars) are typically asymptomatic; however, anal discharge and discomfort can be present.11,12 Rectal C. trachomatis positivity is around 9% in MSM and women 13 ; around 70% of women diagnosed with urogenital C. trachomatis also have rectal infection 14 and this cannot be predicted from a history of anal sex or presence of symptoms in women.13,15 Pharyngeal C. trachomatis infections are also usually asymptomatic, but symptoms of a mild sore throat can occur. 16 Pharyngeal C. trachomatis positivity is between 1% and 3% in both women and MSM and does not appear to be associated with reported oral sex.16–19
Ocular infections
Ocular infections especially with serovars D-K of C. trachomatis can result in conjunctivitis in neonates and adults,2,20–22 and, if untreated, can cause chronic conjunctivitis and persist for several months.
Neonatal infections
Infants born to mothers through an infected birth canal can become colonized and develop chlamydial conjunctivitis and/or pneumonia. 23
Lymphogranuloma venereum (LGV)
LGV is an invasive ulcerative disease caused by the serovars L1-L3 of C. trachomatis. 24
Testing for C. trachomatis in pregnancy [level of evidence: low certainty; Grade 2 recommendation]
C. trachomatis is associated with premature rupture of membranes,29–33 preterm labour and delivery,34–38 chorioamnionitis,30,39 stillbirth,30,35 low birth weight,38,40 congenital infection, 41 neonatal mortality,42,43 as well as infant eye and lung disease (including pneumonia).41,44–46 Transmission occurs in 50%–75% of infants born to mothers with urogenital C. trachomatis; 30–50% of these infants will develop chlamydial conjunctivitis, and 10–20% will develop pneumonia.41,47
Screening and treatment of C. trachomatis infection in pregnancy can prevent the complications noted above. We suggest testing for C. trachomatis is considered in pregnant women, particularly in settings with higher C. trachomatis incidence, as it has the potential to prevent adverse maternal and newborn sequelae.
Laboratory diagnostics
Recommended diagnostic assays
NAATs identifying C. trachomatis-specific nucleic acid (DNA or RNA) in clinical specimens are recommended for diagnosis, due to their superior sensitivity, specificity, and speed [High Certainty; Grade 1].48–65 Only if C. trachomatis NAATs are not available or affordable, should isolation of C. trachomatis in cell culture or identification of C. trachomatis by direct fluorescence assays (DFAs) be used for diagnosis of C. trachomatis infection.
Evidence on the minimum time period between exposure to infection and identification of C. trachomatis on testing is lacking, although clinical experience suggests that a positive NAAT result may be observed within 1–3 days. Patients should be tested when they first present; however, if there is concern about a sexual exposure within the last 2 weeks, they should have a repeat NAAT test 2 weeks after the exposure [Low certainty; Grade 2].
The recommendations from the assay manufacturer should be followed for collection, transportation, and storage of samples, as well as operating the specific assay, including internal controls (positive, negative and, if required in NAATs, inhibition controls) and participation in an appropriate national and/or international external quality assessment (EQA) scheme [High Certainty; Grade 1].
Nucleic acid amplification tests (NAATs)
Due to the high specificity of appropriately validated NAATs, a relatively high prevalence of C. trachomatis in most European settings and risk of not detecting low-positive results in repeated testing, confirmatory testing of NAAT-positive specimens is not recommended [Low certainty; Grade 2].57,66
NAATs should ideally include two targets, including a chromosomal target, as in rare cases C. trachomatis strains lacking the plasmid may not be detected if only a plasmid target is used. 67 Furthermore, laboratories should use NAATs capable of detecting all known C. trachomatis variants68–76 and further investigate any unexplained significant increases or declines in the local incidence or positivity rate [High Certainty; Grade 1].
C. trachomatis NAATs are the preferred test for extra-genital specimens and most commercial NAATs have also been adequately validated for these specimens [High Certainty; Grade 1].63–65,77–82
Point of care tests (POCTs)
Compared to NAATs, the sensitivity of the current, mostly immunochromatographic, tests is substantially inferior.83–89 Accordingly, currently available non-NAAT POCTs do not meet the necessary quality and performance standards to ensure accuracy and reliability, and cannot be recommended in Europe [High Certainty; Grade 1].
Serological testing
Serology is not recommended for screening or diagnosis of acute uncomplicated anogenital C. trachomatis infections [High Certainty; Grade 1]. Nevertheless, when NAATs are not available, detection of specific antibodies to C. trachomatis may support the diagnosis of recent or past invasive infections, such as LGV involving the lymph nodes or neonatal pneumonia (C. trachomatis specific IgM).90–95 Serology might also have limited value in the diagnosis of ascending infections96–98 and for investigation of infertility. 99
Specimen types
Urogenital specimens
The recommended first choice specimens for diagnosis of urogenital C. trachomatis infections with NAATs are first-void urine for men (up to 20 mL, preferably sampled >1 h after previous micturition) and vulvo-vaginal swabs (health-care worker- or self-collected) for women [High Certainty; Grade 1].48,50,52,58,60,100–116 Self-collection of a meatal swab for C. trachomatis NAAT is a reasonable approach for men who are either unable to provide a urine specimen or prefer to collect their own meatal swab over providing urine [Low certainty; Grade 2].61,62,117–119 Non-meatal penile skin swabs are not recommended. 120
If clinical examination is performed, collection of a vulvo-vaginal swab specimen prior to speculum insertion is advised. Due to suboptimal sensitivity, first-void urine for women should only be used if other specimens are not available [High Certainty; Grade 1].48,56,60,121
The use of Pap-smear specimens is not recommended for screening, case finding or other diagnostic purposes, even though several methods to optimize detection in cytological screening specimens have been published [Low certainty; Grade 2].122,123
Self-collection of specimens for C. trachomatis testing
When tested by C. trachomatis NAATs, self-collected vulvo-vaginal, pharyngeal and rectal swabs have been shown to have similar accuracies as sampling by clinicians [High Certainty; Grade 1],100,124–126 and are also highly acceptable among men58,107 and women.58,112,116
Pharyngeal and rectal specimens
The relative low prevalence of pharyngeal-only C. trachomatis (1–3%) and its likely low clinical and public health significance do not provide support for routine universal pharyngeal testing.
Given the higher prevalence of rectal LGV infections in MSM,24,127–130 it is recommended to test for LGV in all MSM who test positive for anorectal C. trachomatis infection with a NAAT performed on a rectal swab, irrespective of the presence of anorectal symptoms [High Certainty; Grade 1]. 131 For additional information, see the latest versions of the “European Guideline on the Management of Lymphogranuloma Venereum” 27 and the “European Guideline on the Management of Proctitis, Proctocolitis and Enteritis Caused by Sexually Transmissible Pathogens”. 131
Semen specimens
Testing of semen specimens is not recommended [High Certainty; Grade 1].
Transgender and gender diverse people
Providers caring for transgender women with a neovagina should have knowledge of their patients’ current anatomy and patterns of sexual behaviour to guide testing and counselling regarding risk. C. trachomatis has been reported in neovaginas that involved penile skin and grafts with urethra mucosa or abdominal peritoneal lining. 132 Gender-based testing for C. trachomatis should be done on the basis of anatomy. No data are available regarding the optimal screening method (urine or vulvo-vaginal swab) for bacterial STIs of the neovagina.
Due to the limited evidence available, we suggest [Low Certainty; Grade 2]: • C. trachomatis NAAT should be performed on a vulvo-vaginal swab and a urine NAAT specimen for transgender women who have had vaginoplasty surgery to maximise detection of any infection. • C. trachomatis NAAT should be performed on a vulvo-vaginal swab specimen for transgender men and non-binary persons with a vagina/cervix who have not had gender affirmation surgery and report having receptive vaginal sex. • If transgender men have undergone metoidioplasty surgery with or without urethral lengthening, irrespective of hook up, a urine specimen will likely be inadequate to detect C. trachomatis; however, it should still be performed. If the person has not had a vaginectomy and practices receptive vaginal sex, then a C. trachomatis NAAT should also be performed on a vulvo-vaginal swab specimen. • If transgender men have undergone phalloplasty surgery, a urine NAAT should be performed. If the person has not had a vaginectomy and practices receptive vaginal sex, then a C. trachomatis NAAT should also be performed on a vulvo-vaginal swab specimen. • Extragenital swab specimens should be tested by C. trachomatis NAAT.
Testing in STI and sexual health clinics including repeat testing
Since most C. trachomatis infections are asymptomatic, the paradigm in C. trachomatis control has long been to proactively screen asymptomatic individuals, to enable timely detection and treatment, and to prevent transmission and complications. However, recent randomised controlled clinical trials found that intensified C. trachomatis screening had no effect on the prevalence of C. trachomatis in the general population.133–135 The evidence for screening asymptomatic individuals to prevent PID is mixed, showing a reduction at the individual level, but no reductions at the population level in practice.136–138 There is also an absence of evidence that screening for C. trachomatis prevents late complications such as infertility 28 and recent estimates suggest that the risk of PID and infertility is considerably lower than previously thought. 139 Therefore, there is a paucity of evidence for screening for asymptomatic C. trachomatis, and an absence of evidence to guide an optimal approach to screening for asymptomatic C. trachomatis. In addition, there are possible harms caused by screening asymptomatic individuals. 28
Countries that consider implementing a reduction in asymptomatic C. trachomatis screening will benefit from dialogue with stakeholders: explaining reasons for change and addressing possible concerns of scaling down testing. Countries should consider using an implementation framework to maximize adoption (involving key populations, health workers, policy makers, and including communication, behavioural change, and implementation theory), as well as having surveillance systems to monitor benefits and harms of test policy changes. 28
The European guidance on testing is formulated here based on the level of evidence and therefore includes suggested advice, rather than strict recommendations. • Annual C. trachomatis testing in STI or sexual health clinics is suggested for all sexually active young females (<25 years of age) [Low certainty; Grade 2]. • Annual C. trachomatis testing in STI or sexual health clinics is suggested for all sexually active MSM [Low certainty; Grade 2].
Pharyngeal C. trachomatis testing
• Routine testing for asymptomatic C. trachomatis infection in the pharynx is not recommended [High certainty; Grade 1].
Rectal C. trachomatis testing
• Annual routine testing for asymptomatic C. trachomatis infection in the rectum is suggested in all sexually active MSM [Low certainty; Grade 2]. • Routine testing for asymptomatic C. trachomatis infection in the rectum in women is not recommended [Low certainty; Grade 2].
Regarding rectal and pharyngeal non-LGV C. trachomatis, both infections have limited associations with sexual risk behaviours and no other risk predictors have been identified to guide selective testing.13,140,141 Therefore, no recommendation to test based on reported sexual risk or other factors is supported by the current evidence [Low certainty; Grade 2].
Management of patients
Information, explanation and advice for the patient
• Patients with a positive C. trachomatis test should be advised to abstain from sexual contact for 7 days after they and their sexual partners have completed treatment and any symptoms have resolved [Low certainty; Grade 2]. • Patients with a positive C. trachomatis test (and their sexual contacts) should be given information about the infection, including details about transmission, prevention and complications. It is recommended that both verbal and written information be provided [Low certainty; Grade 2]. ○ Information for patients is available on the IUSTI Europe website for guidelines (https://iusti.org/wp-content/uploads/2019/11/ChlamydiaLeaflet2017.pdf); • Patients with a positive C. trachomatis test should be advised to test for other STIs, including gonorrhoea, syphilis and HIV [Low certainty; Grade 2]. • MSM with a positive rectal C. trachomatis test should be offered HIV pre-exposure prophylaxis if not already taking it or not known to be living with HIV [Low certainty; Grade 2].
Therapy
Treating C. trachomatis can prevent adverse reproductive health complications and interrupts sexual transmission. Treatment should be provided as promptly as possible, as treatment delays can result in complications such as PID in a proportion of women. 142 Treatment of C. trachomatis-positive sex partners can prevent reinfection as well as onward transmission to other partners. Treatment of pregnant women usually prevents intrapartum transmission of C. trachomatis to neonates.32,143–145
There is still no evidence of any stable, homotypic genetic and phenotypic antimicrobial resistance in C. trachomatis.146–152 However, treatment regimens with azithromycin are less effective than doxycycline for urogenital C. trachomatis infections in men, and for pharyngeal and especially rectal C. trachomatis infections in both sexes.153–155 Clinical failures observed in patients with C. trachomatis treated with azithromycin 1 g single oral dose are of ongoing concern.156–159
Rectal infection
Proportion of doxycycline or azithromycin treated patients with microbiological cure by a negative nucleic acid amplification test for C. trachomatis at 4–6 weeks, by anatomic site, study design, and study population.
a100 mg orally twice per day for 7 days.
b1 g orally single dose.
Azithromycin resistance in Mycoplasma genitalium
Mycoplasma genitalium has emerged as a significant STI and coinfection rates of 3–15% with C. trachomatis have been reported.170–173 A five-day azithromycin treatment regimen is the first-line treatment for M. genitalium infections in Europe. 174 However, macrolide resistance continues to increase in M. genitalium, likely especially due to the widespread use of single-dose azithromycin 1 g to treat other STIs, and the limited availability of diagnostic tests for M. genitalium in many countries. For details regarding treatment of M. genitalium infections in Europe, see the latest version of the “European Guideline on the Management of Mycoplasma genitalium Infections”. 174
Duration of azithromycin regimens
The use of doxycycline to treat C. trachomatis in pregnancy in the absence of a suitable alternative appears to be low risk and should be considered on a case-by-case basis [Low certainty; Grade 2]. 179
Pelvic inflammatory disease (PID)
For detailed and updated information, see the latest version of the “European Guideline for the Management of Pelvic Inflammatory Disease”. 180
C. trachomatis conjunctivitis
Partner notification and management of sexual contact(s)
• Partner notification and testing/treatment should be performed and documented by appropriately trained professionals at the time of diagnosis to improve outcomes [High certainty; Grade 1]. Health care professional-led partner notifications (provider referral) is more effective than patient-led partner notifications (patient referral),
184
although professionals need to be aware of barriers and facilitators in an effective partner notification process.
185
• Sexual contacts should be contacted and testing recommended. Treatment should be offered if C. trachomatis is identified (or if exposure was within the window period for testing). Counselling (as a potential new index patient) for C. trachomatis infection and other STIs should be provided [Low certainty; Grade 2].66,186–189 Treating all sexual contacts empirically risks overuse of antibiotics; recent studies suggest that only between 12% and 64% of contacts to C. trachomatis positive patients test positive for C. trachomatis190–193 and reserving treatment for those in whom C. trachomatis is confirmed can improve antimicrobial stewardship. ○ For male index cases with urethral symptoms: contact all partners since the onset of symptoms, and in the 4 weeks prior to symptom onset [Low certainty; Grade 2].
189
○ For all other index cases (all females, asymptomatic males and those with C. trachomatis at other sites, including rectum, pharynx and eye): contact all partners in the 6 months prior to presentation, or the most recent partner if this was outside the 6-month lookback [Low certainty; Grade 2].66,186,187,189
Where no regulatory barriers exist, expedited partner therapy or patient-delivered partner treatment (PDPT) can be an efficient way to treat partners and reduce infection rates.194–196 However, PDPT should only be implemented as part of a larger system of partner notification strategies. PDPT could be considered as additional tool for specific situations where heath care-provided treatment is not possible. PDPT could also improve partner notification rates when provided in combination with low threshold methods for testing 197 (e.g. home-based sampling and e-healthcare).
For further information, see the latest version of the “European Guidelines for the Management of Partners of Persons with Sexually Transmitted Infection”. 198
Follow-up and test-of-cure (TOC)
A routine TOC is not recommended in patients treated with the recommended first-line regimen of doxycycline 100 mg twice a day for 7 days.
TOC should be performed [Low certainty; Grade 2]: • in pregnancy
199
• in complicated infections • if symptoms persist • if second or third-line regimens have been used • if non-adherence to therapy has occurred • if re-exposure to infection from an untreated partner is suspected
When TOC is indicated, C. trachomatis NAATs should be performed at least 4 weeks after completion of therapy [Low certainty; Grade 2].66,186,187,189,200,201
Repeat infection rates peak at 2–5 months after the initial infection202–206 supporting a recommendation to retest for C. trachomatis within 3–12 months of treatment.66,186,187,189,207 • Repeated testing in 3–6 months should be offered to young women (<25 years of age) who test positive for C. trachomatis [High certainty; Grade 1].
Notification of C. trachomatis cases
C. trachomatis infections should be monitored and registered at the local, regional and national level as mandated by relevant local guidance or statute. The ECDC is responsible for the EU/EEA-wide surveillance of communicable diseases including C. trachomatis infections.
Doxycycline post-exposure propylaxis (PEP)
Doxycycline post-exposure prophylaxis (DoxyPEP) has been evaluated in randomised clinical studies in France208,209 and USA, 210 and significantly reduced the incident cases of syphilis, chlamydia and, in the US study, 210 also gonorrhoea among mostly MSM. Doxycycline 200 mg was taken, by mainly MSM on HIV PrEP and/or living with HIV and who had ≥1 bacterial STI in the recent year, ideally within 24 h (less than 72 h) after condomless sex.208–210 For details regarding DoxyPEP use in Europe, see the “IUSTI Europe Position Statement on Use of DoxyPEP: June 2024”. 211
Footnotes
Author notes
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Evidence was provided by a thorough and systemic review of the literature in the databases Embase.com, Medline (OvidSP), PubMed (articles supplied by publishers not yet indexed in Medline), Web-of-science, Scopus, Cinahl, Cochrane DARE, and Google Scholar. Searches were performed on 28th of July 2021 and updated on 9th of March 2023 and 15th November 2023, and the following broad search terms were used: Chlamydia trachomatis, systematic review, meta-analysis, guideline, protocol. Relevant STI guidelines, including those produced by the World Health Organization, the US Centers for Disease Control and Prevention (https://www.cdc.gov/std/treatment-guidelines/) and the British Association for Sexual Health and HIV (
), were also reviewed.
.
Acknowledgements
The authors are grateful for the valuable input on the guideline to over 100 delegates at the 36th IUSTI Europe Congress (Malta, October 2023) who gave valuable input and feedback on the draft guideline via an online opinion poll. We also thank Dr Tara Suchak from 56 Dean St Clinic, London, UK, for guidance and input on testing advice for transgender and gender diverse people. Finally, we are grateful for comments on the guideline to Werner Aberer, Daniele Colombo, Nicolas Dupin, Derek Freedman, Luísa Graça, Usha Hartgill, Daiva Jasaitiene, Jörgen Skov Jensen, Helle Kiellberg Larsen, Otilia Mårdh, Carle Paul, Miklós Sárdy, Agniezska Beata Serwin, Henry de Vries, Michael Waugh, Ricardo Werner, and Andrew Winter.
Declaration of conflicting interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JW works part time as a Medical Director for Preventx Ltd, a UK-based company providing home sampling tests for blood borne viruses and STIs, including C. trachomatis. JR reports personal fees from GSK Pharma and ownership of shares in GSK Pharma and AstraZeneca Pharma. Other authors: none declared.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
