Chapter 18 ’Lymphogranuloma venereum’, pp. 248–250).Although recognized since antiquity (description of trachoma in Egyptian papyri), the discovery of Chlamydia trachomatis as a cause of genital tract and ocular infections was only made in the early part of the 20th century.
The bacteria species C. trachomatis is divided into four biovars—LGV, trachoma, murine, and swine. These are subdivided into several serovars based on the major outer membrane protein (MOMP) antigens. Serovars D-K of the trachoma biovar are sexually transmissible, commonly referred to as ‘chlamydia infection’, while serovars L1–L3 cause LGV. Genotyping based on MOMP genes refines classification of the species and is a useful research tool.
C. trachomatis is an obligate intracellular pathogen, depending entirely on host cell adenosine triphosphate for its energy. Two distinct structures appear during its life cycle of 48–72 hours.
• Elementary body (0.35 µm): infectious form, attaches to and enters host columnar or pseudostratified columnar cells. After 6–9 hours this transforms into a reticulate body.
• Reticulate body (1 µm): non-infective replicative phase within intra-cellular endosomes. These fuse into an inclusion where reticulate bodies multiply for 24–48 hours. After maturation back into elementary bodies they are released.
WHO estimated the annual worldwide incidence of new infections to be 131 million in 2012. Genital chlamydial infection is the most common bacterial STI in the UK, with the highest incidence amongst 15–24-year-olds, with an estimated prevalence of 1.5–10%. Risk factors for infection include having >1 sexual partner in past year and inconsistent condom use.
• Transmissibility is high: after a single act of unprotected penetrative sex ~10% transmission. Concordance between sexual partners is 75%. Correct use of condoms reduces the risk by ~40%.
• Spontaneous bacterial clearance is estimated to occur in ~20–28% within 3 months and 50% by 12 months. Persistence for up to 6 years has been reported and is believed to be longer in ♀ than ♂.
• Urogenital infection does not result in sustained immunity.
• ♂: urethra (responsible for 35–50% of non-gonococcal urethritis (NGU)); epididymis; prostate (inconclusive evidence).
• ♀: cervix (75–85%); urethra (50–60% overall, 15–20% urethra only); Bartholin’s gland; endometrium; fallopian tubes; vagina if prepubertal.
• Extragenital: conjunctiva; rectum (3–10% in MSM); pharynx (1–2%); hepatic capsule; synovium; rarely endocardium and meninges.
Incubation period is 7–21 days. Up to 50% notice urethral discharge and/or dysuria, while the remainder are asymptomatic.
• Usually mild to moderate opaque or clear urethral discharge.
• Sometimes oedema and erythema of the urethral meatus.
• Often urine ‘threads’: plugs of pus from urethral (Littré’s) glands in FVU, indicating anterior urethritis.
Asymptomatic in up to 80%; symptoms when present include:
• inter-menstrual bleeding, menorrhagia, post-coital bleeding
• usually no abnormal findings
• mucopurulent cervicitis (~33% including asymptomatic): mucopurulent discharge, oedema, congestion, friable (bleeds easily)
• incidental finding on colposcopy of ‘cobblestone’ appearance of the cervix due to raised lymphoid follicles
• cervical ectopy is positively correlated with chlamydial infection.
• ≤Up to 15% of those with proctitis caused by chlamydia (consider LGV Chapter 18 ’Lymphogranuloma venereum’, pp. 248–250).
• ≤Up to 10% + on routine screening (67% without urethral infection).
• Usually asymptomatic (>60%), but may cause anal discharge, pain, discomfort/pruritus, and less frequently rectal bleeding, severe anal pain, tenesmus, and constipation with overt proctitis.
• Occasionally external anal erythema or discharge. Proctoscopy may show mucoid or purulent discharge, erythema, oedema, or friability, even in those who are symptomatic. ‘Cobblestone’ appearance if magnified with a colposcope.
• Up to 5% prevalence (may occur without urogenital infection).
• May occur in women who do not report anal sex
• Usually asymptomatic but symptoms and signs as with ♂.
• MSM up to 2.3% carriage. Limited data for women.
• Usually asymptomatic, but occasionally mild pharyngeal symptoms.
• Concomitant anogenital infection in 60–70%.
• Partners: ~50% ♀ and ~80% ♂ have chlamydia or NGU.
Uni- or bilateral follicular conjunctivitis presents 1–2 weeks after exposure with conjunctival irritation, discharge +/– photophobia/periorbital pain. Signs include conjunctival injection +/– chemosis and ulceration in severe cases, and hyperaemia with follicles 0.5–1 mm in diameter +/– palpebral conjunctival oedema. May cause conjunctival scarring. Epithelial keratitis (unusual) does not cause corneal scarring.
In girls, the vulval and vaginal epithelium are vulnerable to infection. Urethral, pharyngeal, and rectal infections may also occur. Prepubertal infection is a strong indicator of sexual abuse. ▶ However, perinatal C. trachomatis infection may persist for at least 3 years.
Chapter 13, ‘Epididymo-orchitis’, pp. 193–200.
• Sexually acquired reactive arthritis (SARA) or Reiter’s syndrome Chapter 14, ‘Sexually acquired reactive arthritis’ pp. 201–212; polyarthritis affecting mostly weight-bearing joints, usually preceded by urethritis and conjunctivitis in <1% of chlamydial infections.
• Some evidence for association with male infertility.
• Prostatitis and seminal vesiculitis: evidence not well established.
• Pelvic inflammatory disease (PID Chapter 11, pp. 169–179) may occur in about 10–30% of untreated infections, with risk of ectopic pregnancy, infertility, and chronic pelvic pain.
• Bartholinitis +/– Bartholin’s abscess: uni- or bilateral. Pain in vulva with tender cystic swelling of posterior labia majora with erythema. Pus may exude or be expressed from the duct orifice.
• Endometritis: may cause irregular vaginal bleeding.
• Cervical neoplasia: epidemiological and molecular studies show a correlation with chlamydial infection.
• Perihepatitis (Fitz-Hugh–Curtis syndrome): usually found in ♀ with PID suggesting intra-abdominal spread, but also rarely in ♂, implicating lymphatic or haematogenous dissemination.
• SARA ( ‘Complications,’ Men, above, p. 153).
Screening for gonorrhoea and chlamydia in 16–25-year-olds has become part of antenatal care in some areas, and is likely to reduce complications and adverse pregnancy outcomes due to both infections.
The infection rate in pregnancy varies from 2% to 30%. Genital infection is less likely to be complicated by PID (because of thick cervical mucus), but cases of salpingitis have been reported in the 1st trimester.
Chlamydial infection in pregnancy may be associated with preterm delivery and low birth weight.
• Premature rupture of membrane (PROM) more frequent.
• C. trachomatis has been isolated from amniotic fluid.
• Intrapartum pyrexia and late post-partum endometritis 
by 20–25%.
Occurs because of exposure in birth canal during labour.
30–50% of exposed infants acquire chlamydial conjunctivitis, 
to 1–2% if mother treated before delivery. Incubation period 5–14 days (from delivery or PROM), but can be up to 2 months.
Varies from mild (scant mucoid discharge) to severe (profuse discharge) with 67% bilateral involvement. Corneal scarring is rare.
• Nasopharyngeal infection occurs in 70–80% infected neonates, where it is usually asymptomatic.
• 30% with nasopharyngeal infection develop apyrexial pneumonia at 4–12 weeks of age with cough, tachypnoea, and crepitations on auscultation. Apnoeic episodes may occur. Long-term outcome includes impaired lung function and obstructive pulmonary disease.
• Investigations show hyperinflation on radiography, peripheral eosinophilia, and serum immunoglobulins.
• Otitis media complicating nasopharyngeal infection may become chronic if not treated early.
• Vaginal and rectal infection in 10–15% of exposed infants. Usually asymptomatic and may persist for at least 3 years.
See Box 9.1.
Box 9.1 Frequently asked questions
Up to 80% ♀ and 50% ♂ infected with chlamydia are asymptomatic. Therefore, it is possible to be infected for months and, in some cases, years before it is diagnosed.
No. There is no evidence for this.
Yes. There is a very high chance of infection. Screening for STIs is recommended, and treatment to cover chlamydial infection should be taken. It is important not to have sex with your partner until they have been tested/treated in order to prevent re-infection. Even if you use condoms this only reduces the risk of infection, but does not eliminate it. Your partner needs treatment and you need to be retreated.
Although tests for chlamydia are now very reliable, they are not 100% sensitive and, therefore, infection may be missed. In addition, your partner may have received antibiotics for something else or the infection may have cleared spontaneously. Despite conflicting results in a partnership, we recommend treatment for both of you.
Chlamydial infection is extremely common and does not appear to impair fertility in most people who are treated properly. Untreated chlamydia can lead to either symptomatic PID or silent episodes, which are associated with infertility. 90% of couples will conceive within 12 months of trying with regular unprotected intercourse. If you have concerns about your fertility in the future you should seek advice from your GP.
Routine test of cure is not necessary following first-line treatment. If second-line therapy is used, e.g. due to allergy, a test of cure is recommended 3–5 weeks after completing treatment
Light microscopy (×1000) of Gram-stained smear does not show C. trachomatis, but can demonstrate PMNLs:
• Urethral in ♂: 5 PMNL/HPF in the absence of Gram –ve intracellular diplococci suggests NGU.
• Cervical: 30 PMNL/HPF suggests cervicitis.
• Rectal: 1 PMNL/HPF suggests proctitis.
• Urine: 10 PMNL/HPF in threads from first voided urine in ♂ suggests NGU.
• Sterile pyuria may be due to C. trachomatis infection.
• NAATs are the current standard of care test for C. trachomatis. They have high specificity (98–100%) and sensitivity (urine: 85–>95%; cervical swabs: 88–>95%). Suitable for all sites, including self-collected vulvo-vaginal samples. Many assays are now validated for pharyngeal and rectal specimens. If delays >24 hours are anticipated, storage at 4°C is recommended to avoid sample degradation. Manufacturer’s instructions should be followed.
• The most commonly used NAATs amplify by PCR, strand displacement amplification or transcription mediated amplification, using either cryptic plasmid or 23S rRNA.
• New variant C. trachomatis, reported in Scandinavia in 2006 had a deletion in the cryptic plasmid region used for amplification, leading to false negatives. Targets have since been re-designed to prevent evasion of these strains.
• Inhibitory controls are desirable in order to prevent false negatives.
• If the positive predictive value of a reactive result is >90% then confirmatory testing of reactive results is not required. This will depend on local prevalence, as well as sensitivity and specificity of the assay. If confirmatory testing is required, this can be done by repeating the test or by using a different target/platform.
EIA, direct fluorescent antibody (DFA), and cell culture have all be used for screening in the past, but are no longer recommended due to lower sensitivity and specificity, and poorer performance when compared with NAATs. Other DNA probe methods are now rarely used. Serum antibody tests, which use micro-immunofluorescence to detect species-specific antibody, are not routinely available and are of limited use as mucosal infections do not elicit a strong antibody response, and they are only useful for retrospective diagnosis. IgG titre >1:64 may indicate recent infection, IgA may indicate active infection and IgM may be useful in diagnosis of neonatal pneumonia.
Not yet used as routine in most settings due to reduced sensitivity and specificity compared with laboratory-based methods. New EIA-based POCT have sensitivities up to 93% (aQcare Chlamydia TRF kit). NAAT-based POCTs are being developed for genital sampling and look promising.
• Vulvo-vaginal swab (VVS), either self-taken or by HCW is the preferred method, with 96–98% sensitivity. Self-sampling reported higher acceptability than urine or cervical specimens.
• Endocervical specimens are less sensitive than VVS.
• FVU is less sensitive than VVS in women, but has equivalent sensitivity to urethral sampling and are preferred in men.
• Urethral swabs should be inserted 2–4 cm. Self-taken penile meatal swabs have shown good results, but are less acceptable.
• Extra-genital samples have variable sensitivities depending on the platform used:
• rectal swabs can be taken blind, via proctoscopy or self-taken
• pharyngeal swabs can be self-taken by HCW.
• Pooling of samples from different sites reduces costs. Local validation is required, as sensitivity may be reduced. The site of infection would not be known if the result was reactive.
• Men and women with proctitis, and all MSM with HIV and C. trachomatis at any site should have samples tested for LGV.
NAAT is the recommended detection method. Chlamydia culture is no longer recommended. Samples should be taken from all sites of penetration. Reactive results should be confirmed using a different target.
▶ Advise avoidance of any sexual contact, including with condoms, until the patient and partner(s) have completed treatment or 7 days after single dose azithromycin, and symptoms have resolved
▶ Patient should be given verbal and written information regarding natural history, transmission, treatment, and complications.
• All patients diagnosed with C. trachomatis should be offered screening for other STI.
• Retesting after window periods for bacterial and viral STI should be recommended.
For PID Chapter 11, ‘Pelvic inflammatory disease’, pp. 169–179, and Chapter 13, ‘Epididymo-orchitis’, pp. 193–200.
• doxycycline 100 mg bd for 7 days (do not use if pregnant)
• azithromycin 1 g followed by 500 mg daily for further 2 days
• erythromycin 500 mg bd for 10–14 days or
• ofloxacin 200 mg bd or 400 mg od for 10–14 days.
• Recommended treatment: doxycycline 100 mg bd for 7 days.
• Alternative treatment (TOC recommended): azithromycin 1 g single dose, or ofloxacin (risk of C. difficile and tendon rupture), or erythromycin ( effective, side effects, daily dosing).
Treat as for genital infection
Tetracyclines, fluroquinolones, and co-trimoxazole are contraindi-cated, including doxycycline and ofloxacin.
• Azithromycin: 1 g followed by 500 mg daily for further 2 days. Adverse pregnancy outcomes unlikely but lack of data.
• Erythromycin: 500 mg bd 14 days or 4 times daily for 7 days.
• Amoxicillin: 500 mg tid for 7 days (better tolerated than erythromycin).
• Test of cure recommended for all women treated in pregnancy.
Infants born to mothers with untreated chlamydial infection should be monitored for signs of infection and/or given epidemiological treatment. Swabs should be taken for C. trachomatis NAAT testing from everted eyelids 5–10 days after birth, and nasopharynx if chlamydial pneumonia suspected.
• erythromycin: 50 mg/kg oral daily divided into 4 doses for 14 days or
• azithromycin: 20 mg/kg oral daily in single dose for 3 days
• topical treatments are ineffective.
• erythromycin: 50 mg/kg oral daily (up to 1 g) divided into 4 doses for 14 days or
• if weight ≥45 kg: azithromycin 1 g as a single dose or
• if weight ≥45 kg and ≥8 years old: doxycycline 100 mg bd for 7 days.
PN should be discussed with all index cases at the time of diagnosis.
All confirmed contacts should be offered full STI screen, including HIV, and offered epidemiological treatment.
Contact tracing period for the following index cases:
• Men with symptomatic urethritis: all contacts since onset and 4 weeks prior to onset of symptoms.
• All others: 6 months prior to presentation.
Similar principles should apply to the mother of neonate with chlamydial infection and her sex partner(s).
• Re-testing recommended after 3–6 months for patients <25 years old due to high re-infection rate.
• A test of cure following treatment of urogenital C. trachomatis infection, if not pregnant, is only recommended if not treated with doxycycline or azithromycin, symptoms persist, adherence issues.
• Repeat treatment if risk of re-infection from untreated partner.
• If persistent symptoms check compliance.
• Re-testing (if required) should be delayed until at least 3–5 weeks after the end of the treatment, to avoid false positive result
Chlamydial infection facilitates HIV transmission, producing in detectable virus in urethral/cervical secretions when infection is present. This is reversed following antibiotic treatment.
LGV prevalence in this patient group, so all diagnosed with rectal chlamydia should either be tested for LGV, treated presumptively with 21 days doxycycline 100 mg bd, or have TOC.
Further information
British Association for Sexual Health and HIV Chlamydia guideline 
https://www.bashh.org/guidelines