Chlamydia

Chlamydia trachomatis is an obligate intracellular bacterium with a biphasic life cycle (extracellular elementary body, intracellular reticulate body). It is the commonest bacterial sexually transmitted infection worldwide, with over 130 million new cases yearly.

Serovars and diseases:

• Serovars D to K: genital infection (urethritis, cervicitis, pelvic inflammatory disease, epididymitis, proctitis), neonatal conjunctivitis and pneumonia, and adult inclusion conjunctivitis.
• Serovars L1, L2, L3: lymphogranuloma venereum (LGV), an invasive lymphatic infection.
• Serovars A to C: trachoma, the leading infectious cause of blindness.

Epidemiology:

• Highest prevalence in sexually active young women (15 to 24 years: 3 to 5% prevalence) and young men. Many infections are asymptomatic: up to 70% in women and 50% in men. Reinfection is frequent.
• Risk factors: age under 25, new or multiple partners, inconsistent condom use, previous STI, MSM, and partner with chlamydia.
• Untreated infection resolves in about 50% within a year, but persistent infection leads to upper tract disease.

Complications:

• Women: cervicitis, pelvic inflammatory disease (10 to 15% of untreated infections), tubal factor infertility, ectopic pregnancy, chronic pelvic pain, perihepatitis (Fitz-Hugh-Curtis syndrome), urethral syndrome, and adverse pregnancy outcomes (preterm delivery, premature rupture of membranes).
• Men: urethritis, epididymo-orchitis, prostatitis, proctitis, reactive arthritis (sexually acquired reactive arthritis), and possible reduced semen quality.
• Neonates: conjunctivitis (5 to 14 days after birth) and pneumonia (4 to 12 weeks), in 20 to 50% and 10 to 20% of exposed infants respectively.
• Increased risk of HIV acquisition and transmission, and HPV persistence with cervical neoplasia.

Most infections are asymptomatic.

Women (symptomatic in 20 to 30%)

• Mucopurulent cervical discharge, post-coital and intermenstrual bleeding, dysuria, frequency, and lower abdominal pain. Cervix appears friable with mucopurulent endocervical exudate (more than 10 white cells per high-power field), or normal.
• Upper tract disease (PID): pelvic pain, dyspareunia, irregular bleeding, fever, cervical motion, uterine and adnexal tenderness. Often subclinical (silent PID), causing infertility.
• Fitz-Hugh-Curtis syndrome: right upper quadrant pain, pleuritic, with liver capsule inflammation.

Men (symptomatic in 30 to 50%)

• Dysuria with scant mucoid or watery urethral discharge, urethral itching or irritation, usually 1 to 3 weeks after exposure. Epididymitis (unilateral testicular pain and swelling, fever).
• Rectal infection: usually asymptomatic. May cause rectal pain, discharge and tenesmus.
• Pharyngeal infection: usually asymptomatic.

Reactive arthritis: asymmetrical oligoarthritis (knees, ankles), enthesitis, dactylitis, conjunctivitis, urethritis, circinate balanitis, keratoderma blenorrhagicum, onset 1 to 4 weeks after infection, HLA-B27 association.

Neonates and others: neonatal conjunctivitis (mucopurulent discharge, eyelid swelling), pneumonia (staccato cough, tachypnoea, afebrile, eosinophilia, interstitial infiltrates). Adult inclusion conjunctivitis (follicular conjunctivitis).

Red flags: pelvic inflammatory disease, pregnancy, epididymo-orchitis, sexual assault, reactive arthritis, children (consider abuse), and treatment failure.

Nucleic acid amplification tests (NAAT) are the standard (sensitivity 90 to 99%, specificity above 99%):

• Women: vulvovaginal swab (self-collected acceptable, preferred specimen), endocervical swab, or first-void urine (slightly less sensitive).
• Men: first-void urine (first 20 to 30 mL, at least 1 hour after last void), or urethral swab.
• Extragenital sites: rectal and pharyngeal swabs (NAAT validated in most laboratories) in people reporting receptive anal or oral sex.
• Neonates: conjunctival swab (NAAT or culture, scrape cells), nasopharyngeal aspirate for pneumonia.
• LGV testing (serovar determination) in rectal chlamydia of MSM or symptomatic proctitis, and in patients with buboes.
• Culture and direct fluorescent antibody are of lower sensitivity and used for legal cases (child abuse, sexual assault where culture is required).

Screening

• Annual screening of all sexually active women under 25, women over 25 with new or multiple partners, MSM at exposed sites (every 3 to 6 months if at risk), pregnant women at first antenatal visit (and in the third trimester if under 25 or at risk), and people with HIV.

Other tests: HIV, syphilis, gonorrhoea, hepatitis B/C, trichomonas, pregnancy test, and pelvic ultrasound if PID or tubo-ovarian abscess. Laparoscopy rarely, for diagnosis of PID or infertility evaluation. Serology has no role for diagnosis (except LGV and infertility research).

Tests of cure: not routinely recommended after doxycycline, but advised in pregnancy (4 weeks after treatment), when compliance is uncertain, symptoms persist, after rectal infection treated with azithromycin, or an alternative regimen. NAAT may remain positive up to 3 to 4 weeks after completing treatment because of residual nucleic acids, so test no earlier than 4 weeks.

Uncomplicated genital, rectal or pharyngeal chlamydia (non-pregnant adults and adolescents)

• Doxycycline 100 mg orally twice daily for 7 days (first line, higher microbiological cure than azithromycin, especially for rectal infection, 99% vs 83%).
• Alternatives: azithromycin 1 g orally as a single dose (or 500 mg then 250 mg daily for 4 days), levofloxacin 500 mg daily for 7 days, or ofloxacin 300 mg twice daily for 7 days.
• Pharyngeal chlamydia: doxycycline 100 mg twice daily for 7 days.

Pregnancy and breastfeeding

• Azithromycin 1 g orally single dose (first line), or amoxicillin 500 mg three times daily for 7 days. Erythromycin 500 mg four times daily for 7 days (poorly tolerated). Doxycycline, ofloxacin and levofloxacin are contraindicated. Test of cure at 4 weeks and retest at 3 months and in the third trimester.

Pelvic inflammatory disease

• Outpatient: ceftriaxone 500 mg IM single dose, plus doxycycline 100 mg orally twice daily for 14 days, plus metronidazole 400 to 500 mg orally twice daily for 14 days.
• Inpatient (severe illness, pregnancy, tubo-ovarian abscess, failure to respond within 72 hours, inability to take oral therapy): ceftriaxone 1 to 2 g IV daily plus doxycycline 100 mg IV or oral twice daily plus metronidazole 500 mg IV every 8 hours, switching to oral therapy 24 hours after clinical improvement to complete 14 days. Alternative: clindamycin 900 mg IV every 8 hours plus gentamicin 5 mg/kg daily. Drain tubo-ovarian abscess if no response. Remove an intrauterine device only if there is no clinical improvement (it can remain in situ with treatment).

Epididymo-orchitis (men under 35 or at risk of STI)

• Ceftriaxone 500 mg IM single dose plus doxycycline 100 mg twice daily for 10 to 14 days. In men who practice insertive anal sex, add coverage for enteric organisms (ofloxacin 300 mg twice daily or levofloxacin 500 mg daily for 10 days). Scrotal support, NSAIDs, and exclusion of testicular torsion.

Neonatal infection

• Conjunctivitis and pneumonia: oral azithromycin 20 mg/kg daily for 3 days, or erythromycin ethylsuccinate 50 mg/kg/day in 4 divided doses for 14 days (monitor for infantile hypertrophic pyloric stenosis, a small risk with macrolides in the first 6 weeks, particularly erythromycin). Topical therapy alone is inadequate. Treat the mother and her partner(s). Prophylaxis with erythromycin 0.5% ointment is of limited efficacy against chlamydia.

Reactive arthritis

• NSAIDs (naproxen 500 mg twice daily, indomethacin 25 to 50 mg three times daily), intra-articular corticosteroids, treat triggering infection (doxycycline 100 mg twice daily for 3 months has some evidence), and sulfasalazine 2 to 3 g daily or methotrexate for persistent disease.

Partner management and prevention

• Notify and treat all sexual partners from the previous 60 days (or the most recent partner if longer). Expedited partner therapy (supplying medication to partners without examination, where legal). Abstain from sexual intercourse until 7 days after the patient and partners complete treatment (single-dose) or until a course is finished and symptoms resolved.
• Retest at 3 months (or at first visit within 12 months) in all treated people, because reinfection occurs in 10 to 20%.
• Screen and treat other STIs, HIV counselling, offer HIV PrEP to at-risk people, doxycycline post-exposure prophylaxis for selected MSM, vaccination (HPV, hepatitis B), and condom promotion.
• Screening programmes for young women reduce PID incidence by about 50%.

Follow-up

• Review symptoms 1 to 2 weeks after therapy if persistent. Treatment failure should prompt consideration of non-adherence, reinfection, M. genitalium, and other causes. Infertility evaluation for women with prior PID (hysterosalpingography), and early referral for assisted reproduction.