Chlamydia trachomatis (CT) is a gram-negative, obligate intracellular bacterium with a unique biphasic life cycle. It is considered the leading bacterial cause of sexually transmitted infections worldwide and is also the leading cause of preventable blindness.^1,2 It is composed of three biovars: Trachoma, genital tract, and lymphogranuloma venereum (LGV). These biovars are further categorized into serovars, distinguished by differences in major out membrane proteins (MOMPs), epitopes that can be detected using monoclonal antibodies.¹ The trachoma biovar (serovars A-C) is associated with ocular disease, the genital tract biovar (serovars D-K) primarily with sexually transmitted infection, and the LGV biovar (serovars L1-3) with invasive urogenital or anorectal disease.^1,2

CT is the most prevalent bacterial cause of sexually transmitted disease in the U.S. and globally. In 2020, the WHO estimated 128.5 million new CT infections among adults aged 15 to 49 yr.³ In 2022, the CDC identified 1.65 million new CT infections, with rates of reported infection increasing by 1.8% in males and decreasing by 1.2% in females.⁴ About 1.8 million cases were reported in 2019.⁴ CT infection is often asymptomatic, and estimates of prevalence are likely lower than reality. CT is most prevalent in younger individuals, and 57.7% of new CT cases in the U.S. were among those 15 to 24 yr of age.⁴

The majority (70% to 80%) of CT infections in females are asymptomatic; however, untreated infections can have significant consequences. Manifestations of CT infection include cervicitis, acute urethral syndrome, endometritis, and pelvic inflammatory disease (PID).^5,6

Ascending genital infection (PID) is estimated to occur in 10% to 20% of women with untreated CT and confers a risk of sepsis, tubal infertility, ectopic pregnancy, and chronic pelvic pain.^7,8 Additionally, untreated CT increases an individual’s risk of acquiring HIV if exposed.⁸

On exam, women with CT infection may have no signs; however, purulent discharge and cervical friability (caused by inflammation of endocervical columnar epithelium) can occur. PID is a clinical diagnosis, confirmed by findings of pelvic pain with cervical motion, adnexal, or uterine tenderness on exam. A less frequent manifestation of PID is a result of ascending intraabdominal infection, perihepatitis, also referred to as Fitz-Hugh-Curtis syndrome.

In men, most infections are asymptomatic but can result in mucopurulent discharge, urethritis, prostatitis, or epididymitis. Prostatitis may present as urinary dysfunction, pain with ejaculation, and pelvic pain. Epididymitis manifests as unilateral testicular pain and swelling and in rare cases can result in infertility.⁹

• Sexually transmitted inclusion conjunctivitis can develop as a consequence of conjunctiva exposed to infected genital secretions. Common symptoms include blurred vision, foreign body sensation, watery discharge, and redness of the eyes. Symptoms may be mistaken for environmental allergies.¹⁰
• CT infection can also cause proctitis or infection of the rectum in men and women. This usually presents with rectal pain, discharge, or bleeding. CT infection of the throat is usually asymptomatic in both men and women and not a usual cause of pharyngitis. Aseptic, reactive arthritis is a rare, self-limiting complication of CT infection that is more common in men.^5,8
• Infants born to women with untreated CT are at risk of conjunctivitis and pneumonia.⁸ Neonatal conjunctivitis onset is typically 5 to 12 days after birth, while a subacute pneumonia, often in the absence of fever, develops at 1 to 3 mo of age.^8,9

Clinical manifestations and sequelae of Chlamydia trachomatis urogenital infections and patterns of transmission are illustrated in Fig. 1. Table 1 summarizes clinical characteristics of common C. trachomatis infections.

Figure 1 Clinical Manifestations and Sequelae of Chlamydia Trachomatis Urogenital Infections and Patterns of Transmission

(From Bennett JE et al: Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, ed 9, Philadelphia, 2020, Elsevier.)

Chlamydia trachomatis is an obligate, intracellular bacteria. At the time of exposure, CT exists in the extracellular, transmissible form called elementary body (EB). Infected epithelial cells release inflammatory mediators and chemokines that trigger an influx of leukocytes including lymphocytes, macrophage, and eventually plasma cells. Fibroblast proliferation, mediated by Th1 and Th17 cell types, results in scar tissue formation associated with tubal factor infertility.^7,11 Within 6 to 8 h of entering the host cell, CT reorganizes into a reticulate body (RB) that reproduces by binary fission.⁵

Differential diagnosis depends on presenting symptoms. Some of the common differentials are listed in the following:

• •Candidiasis
• •Conjunctivitis
• •Ectopic pregnancy
• •Endometriosis
• •Gonorrhea
• •Mycoplasma infection
• •Pelvic inflammatory disease
• •Trichomonas
• •Urethritis
• •Urinary tract infection

Individuals with signs and symptoms mentioned previously should be screened for CT infection. Since CT infection is often asymptomatic, routine screening plays a key role in diagnosis and prevention. The CDC recommends annual screening for sexually active females <25 yr of age. There is currently no routine screening recommendation for men; however, all young men who have sex with men (YMSM) should be screened annually.⁸ Pregnant women should be screened at initial prenatal encounter and again in the third trimester.

Screening interval is generally determined by the presence of risk factors such as: Acquiring a new sexual partner, multiple partners, occupational hazard, or having a history of sexually transmitted infection.

• NAATs are the gold standard for diagnosis because of their high sensitivity and specificity for the detection of CT infection. CLIA-approved NAAT exists for most specimen sources.⁸
• Vaginal swabs are more sensitive than urine for the detection of CT and are often preferred.¹² The sensitivity of vaginal swab vs. urine for CT has been estimated as 94.1% vs. 86.9%.¹³ For best results, urine collection should be completed with a first-void urine sample. Self-collected vaginal swab samples for women have the same sensitivity and specificity as provider-collected samples.¹⁴
• Microscopy should not be used for CT diagnosis; however, >10 white blood cells per high-power field with a mucopurulent discharge is likely suggestive of infection.

Doxycycline 100 mg PO bid for 7 days

Refer to infectious disease specialist if persistent infection or gynecologist if salpingitis is suspected.

• •Doxy PEP, or a preventive treatment regimen of doxycycline, is now recommended by the CDC for high-risk populations (including men who have sex with men [MSM] and transgender women [TGW]) who have had a bacterial STI in the last year.¹⁵
• •Doxycycline PEP has demonstrated benefit in reducing incident syphilis, chlamydia, and gonorrhea in certain populations and represents a new approach to addressing STI prevention in MSM and TGW at increased risk for these infections. The CDC recommends that providers counsel gay, bisexual, and other MSM and TGW with a history of at least one bacterial STI (specifically syphilis, chlamydia, or gonorrhea) during the past 12 mo about the benefits and harms of using doxy PEP (Table 2). Although the pharmacokinetics of doxycycline and experience in treating bacterial STIs suggest that doxy PEP should be effective in other populations, clinical data to support doxy PEP in other populations (i.e., cisgender women, cisgender heterosexual men, transgender men, and other queer and nonbinary persons assigned female at birth) are limited. As a result, providers should use their clinical judgement and shared decision-making to inform use of doxy PEP with populations that are not part of the CDC recommendations. If doxy PEP is prescribed, the provider should write the prescription for self-administration of the recommended dose of 200 mg of doxycycline (any formulation) to be taken as soon as possible within 72 h after having oral, vaginal, or anal sex with a maximum dose of 200 mg every 24 h. The prescription should account for enough doses on the basis of the person’s anticipated sexual activity until their next visit. Ongoing need for doxy PEP should be assessed every 3 to 6 mo. Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach (Box 1), including risk reduction counseling; STI screening and treatment; recommended vaccination; and linkage to HIV PrEP, HIV care, or other services as appropriate.¹⁵ Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3 to 6 mo thereafter. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.¹⁵

• Cervicitis (Related Key Topic)
• Urethritis, Gonococcal (Related Key Topic)
• Gonorrhea (Related Key Topic)
• Urethritis, Nongonococcal (Related Key Topic)
• Pelvic Inflammatory Disease (Related Key Topic)
• LGV (Related Key Topic)