Definition, Etiology, PathogenesisTop
1. Etiologic agent: Chlamydia trachomatis, bacterium of the genus Chlamydia. There are >10 serovars of C trachomatis, which cause a variety of diseases. Serovars D to K (non–lymphogranuloma venereum [non-LGV] serovars) are the cause of nongonococcal chlamydial lower genitourinary tract infections, proctitis, pharyngitis, and conjunctivitis, as well as complications of these, while serovars L1, L2, and L3 are the etiologic agents of LGV. Serovars A to C cause endemic conjunctivitis (trachoma).
Chlamydiae are obligate intracellular bacteria. They have 2 morphologic forms: the elementary body (a metabolically inactive extracellular form with a plasma membrane) and the reticulate body (a metabolically active and replicating intracellular form). The elementary body has the ability to infect epithelial cells.
2. Pathogenesis: C trachomatis (serovars D-K) mainly infects columnar epithelium–lined mucous membranes that have direct contact with infectious secretions (the most common sites of infection are the urethra, cervical canal, anus, throat, and conjunctiva), while areas lined with multilayered squamous or transitional epithelium are less susceptible. Infection occurs at the site of elementary body attachment to an epithelial cell. The elementary body enters the cell through endocytosis and, once in the cell, loses the cell membrane, replicates, and together with other reticulate bodies forms an inclusion body. As the inclusion body increases in size, the host’s cell is destroyed, and reticulate bodies reorganize into elementary bodies with the ability to infect further epithelial cells.
3. Reservoir and transmission: The reservoir is humans. Infection is transmitted primarily through direct contact of the mucous membrane (lined with columnar epithelium) with infectious secretions during sexual contacts (genito-genital, genito-anal, oral-genital, or oral-anal) or delivery. Indirect transmission, eg, through objects, is suggested to be possible in rare cases.
4. Risk factors: Young age (15-29 years), high sexual activity, multiple sexual partners, promiscuity, living in large agglomerations, low socioeconomic status, illicit drug use, nonuse of condoms, presence of foreskin, other sexually transmitted infections (STIs).
5. Incubation and contagious period: The incubation period is 7 to 21 days (usually 10-12 days). Infectivity during sexual contacts is high and the risk of infection transmission between sexual partners may reach 75%.
Clinical Features and Natural HistoryTop
1. C trachomatis infection in men: The most common type of C trachomatis infection in men is nongonococcal urethritis, which is asymptomatic in 50% of cases.
2. C trachomatis infection in women: The most common type of C trachomatis infection in women is cervicitis, which is usually asymptomatic (>90%). Secondary urethritis develops in <50% of cases and is also predominantly asymptomatic. Manifestations (if present) include vaginal discharge, typically mucous or mucopurulent (30%); ectocervical swelling, redness, and easy bleeding; and dysuria (if the urethra has been affected).
3. C trachomatis infection in both sexes:
1) Chlamydial proctitis typically occurs in women secondarily to cervicitis and urethritis or as a primary infection resulting from anal sexual contacts in women and in men who have sex with men (MSM). Symptoms vary in severity from asymptomatic disease to severe proctitis. Severe proctitis is usually caused by C trachomatis serovar L (anorectal LGV). Proctitis due to infection with serovars D to K (~75% cases) is usually milder. Manifestations include small amounts of mucous or mucopurulent anal discharge, perianal pain or burning sensation, bleeding during defecation.
2) Chlamydial pharyngitis is rare and typically asymptomatic; infection is usually transmitted during oral-genital sexual contacts.
4. C trachomatis infection in newborns and infants: Infection is usually transmitted from the mother to a newborn during delivery. Types of infection:
1) Conjunctivitis: Mostly asymptomatic or with mild symptoms. The onset of symptoms is usually between days 5 and 14 of life. Symptoms include conjunctival irritation or, in more severe cases, eyelid redness and swelling with mucopurulent discharge. The infection may resolve spontaneously within a few months. Complications are rare.
2) Pneumonia: C trachomatis is a frequent etiologic agent of pneumonia in infants. Symptoms occur in week 4 to week 11 of life and include pharyngitis, cough, difficulty breathing, and tachypnea. Laboratory studies often reveal eosinophilia with white blood cell count within normal range. Coexisting or past conjunctivitis is frequent.
Identification of the etiologic agent:
1) Molecular tests: The nucleic acid amplification test (NAAT) has the highest sensitivity (similar in symptomatic and asymptomatic infections) and specificity, and is therefore the preferred study. The specimen of choice in men is a first pass of urine (passed >1 h from last miction), and in women, vaginal or cervical swab. Due to low sensitivity, a first pass of urine in women can be used as a specimen for testing only if other specimens cannot be obtained.
2) Direct immunofluorescence: Detection of C trachomatis elementary bodies in specimen smears examined with a fluorescence microscope.
3) Culture on McCoy cells: Detection of C trachomatis inclusions inside cells inoculated with the specimen studied. As this is a time-consuming, labor-intensive, and expensive test, it is not routinely used in diagnostic workup of chlamydial infections. However, because of its 100% specificity, it is the test of choice for verification of positive results obtained with other methods.
Diagnosis is based on patient history (high-risk sexual behaviors), clinical features, and laboratory test results.
1. Chlamydial urethritis: Gonococcal urethritis, nongonococcal urethritis of other etiology (Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas vaginalis), urethritis caused by mechanical injuries, genital herpes, venerophobia.
2. Chlamydial cervicitis: Gonococcal cervicitis and urethritis, genital herpes, vulvovaginal candidiasis, bacterial vaginosis, trichomoniasis, cervical cancer.
3. Chlamydial proctitis: Proctitis in other STIs, proctitis caused by gram-negative intestinal bacilli (particularly in MSM), protozoal proctitis (Entamoeba histolytica), anorectal candidiasis, anal cancers.
4. Chlamydial pharyngitis: Gonococcal pharyngitis, viral or bacterial pharyngitis.
C trachomatis is very rarely resistant to antibiotics, which is why empirical treatment can be used. Suspect infection with a resistant strain if there is no response to treatment, having excluded reinfection and patient nonadherence. Do not routinely perform NAATs as a test of cure (TOC) in patients who received the recommended first-line treatment. Perform a NAAT after 4 weeks of treatment completion in the following cases:
1) Persistent symptoms of infection.
2) Patients treated with second- or third-line agents.
3) Suspected nonadherence.
4) Suspected reinfection.
6) Complicated infection.
A repeat test should be performed 3 to 6 months post treatment in young women and men (aged <25 years) to exclude reinfection.
1. Treatment of uncomplicated genitourinary tract infections:
1) First-line treatment: Oral doxycycline 100 mg bid for 7 days or oral azithromycin 1 g in a single dose.
2) Second-line treatment (perform a TOC upon treatment completion): Oral erythromycin 500 mg bid for 7 days, oral levofloxacin 500 mg bid for 7 days, or oral ofloxacin 200 mg bid for 7 days.
3) Third-line treatment (perform a TOC upon treatment completion): Oral josamycin 500 mg tid or 1000 mg bid for 7 days.
2. Treatment of uncomplicated proctitis or pharyngitis due to infection with non-LGV C trachomatis serovars: Use oral doxycycline 100 mg bid for 7 days (preferred in proctitis) or oral azithromycin 1 g in a single dose (perform a test-of-cure assay upon treatment completion in patients with proctitis).
3. Treatment of uncomplicated genitourinary tract infections during pregnancy and breastfeeding:
1) First-line treatment: Oral azithromycin 1 g in a single dose.
2) Second-line treatment: Oral amoxicillin 500 mg tid for 7 days or oral erythromycin 500 mg qid for 7 days.
3) Third-line treatment: Oral josamycin 500 mg tid or 1000 mg bid for 7 days.
Perform a TOC upon completion of treatment.
4. Treatment of C trachomatis conjunctivitis: Use 1 g of oral azithromycin in a single dose or 100 g of oral doxycycline bid for 7 days.
1. Complications in men:
1) Epididymitis: C trachomatis is the most common cause of epididymitis in men aged <35 years. Manifestations usually develop weeks after the onset of urethritis, and the disease is typically unilateral. Signs and symptoms include pain radiating to the groin, enlarged epididymis, edema and redness in the scrotum, and/or fever, and are usually less pronounced than in gonococcal epididymitis.
2) Prostatitis: Very rare; usually mild, with periodically recurrent symptoms.
3) Urethral stricture: Currently rare.
2. Complications in women:
1) Pelvic inflammatory disease (PID): Chlamydial infections are the most common cause of PID in Europe. Endometritis is present in <50% of women with chlamydial cervicitis, typically with mild symptoms. The most common manifestations are intermenstrual bleeding, prolonged or heavy menstrual bleeding, hypogastric pain or tenderness. The infection may spread to adnexa. Manifestations of PID associated with chlamydial infection resemble those of gonorrhea. Serious sequelae of chlamydial PID include infertility and extrauterine pregnancy (the risk is higher than in patients with gonorrhea).
2) Bartholinitis and skenitis are rare complications of cervicitis.
3. Complications in both sexes:
1) Reiter syndrome: Present in 1% to 3% of men with nongonococcal urethritis; less prevalent in women. The classic triad of symptoms includes reactive arthritis, conjunctivitis, and urethritis or cervicitis. Currently Reiter syndrome is defined as reactive arthritis lasting ≥1 month and preceded by or coexisting with urethritis or cervicitis. The arthritis usually affects knees and ankles. Approximately 20% of patients have psoriasis-like skin and mucosal lesions, often localized on the hands, feet, glans, or vulva.
2) Fitz-Hugh-Curtis syndrome (see Gonorrhea).
C trachomatis infections in pregnancy are risk factors for premature birth and for conjunctivitis and pneumonia in newborns and infants. Screening for chlamydial infections is recommended in pregnancy, especially in populations with high prevalence of those infections (>5%).
In early disease and in patients with early initiated treatment, the prognosis is good. In patients with complications the response to treatment and prognosis are worse.
Immunoprophylaxis: None available.
1. Avoiding high-risk sexual behaviors, using condoms.
2. Every patient with diagnosed chlamydial infection should be offered specialist counseling and recommended sexual abstinence until completion of treatment and resolution of symptoms.
3. Contact investigation: Obtain information on the patient’s sexual contacts and try to offer them proper diagnostic workup, treatment, and counseling.
4. Patient isolation: Not required.
5. Personal protective equipment (PPE) for medical staff: Standard.