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Clinical manifestations and diagnosis of Chlamydia trachomatis infections

Clinical manifestations and diagnosis of Chlamydia trachomatis infections
Author:
Katherine Hsu, MD, MPH, FAAP
Section Editor:
Jeanne Marrazzo, MD, MPH, FACP, FIDSA
Deputy Editor:
Allyson Bloom, MD
Literature review current through: Dec 2022. | This topic last updated: Apr 08, 2022.

INTRODUCTION — Chlamydia trachomatis is the most common bacterial cause of sexually transmitted genital infections [1]. The majority of affected persons are asymptomatic and, thus, provide an ongoing reservoir for infection. In infants born to mothers through an infected birth canal, conjunctivitis and pneumonia can occur. Moreover, both males and females can experience clinical syndromes due to infection at common epithelial sites, including the rectum and conjunctivae. Other types of C. trachomatis infection, including lymphogranuloma venereum and endemic trachoma, an ocular infection spread by direct contact and seen commonly in the developing world, may occur in both males and females.

The clinical manifestations and diagnosis of C. trachomatis in females and males are discussed below. The epidemiology and treatment of C. trachomatis, as well as neonatal C. trachomatis infection, lymphogranuloma venereum, and endemic trachoma, are discussed in detail elsewhere. (See "Epidemiology of Chlamydia trachomatis infections" and "Treatment of Chlamydia trachomatis infection" and "Chlamydia trachomatis infections in the newborn" and "Lymphogranuloma venereum" and "Trachoma".)

Screening for chlamydia and other sexually transmitted infections is also discussed elsewhere. (See "Screening for sexually transmitted infections".)

INCUBATION PERIOD AND ASYMPTOMATIC PERSISTENCE — The incubation period of symptomatic disease ranges from 5 to 14 days following infection. However, it is unclear how long those with asymptomatic disease may carry the infection.

In a systematic review of 10 studies of untreated, uncomplicated genital chlamydial infections, detection of chlamydia persisted over the short term (weeks to months after diagnosis) in 56 to 89 percent and for at least one year in 46 to 57 percent [2]. However, these studies did not record infection date nor did they evaluate for reinfection as opposed to persistent infection, thus limiting the understanding of duration of untreated chlamydial infection. Subsequent modeling studies have hypothesized that chlamydial infections are less likely to become established but, once established, clear slowly, and more slowly in males than in females (mean untreated infection duration of 2.84 and 1.35 years in males and females, respectively) [3,4].

Nevertheless, despite the possibility of spontaneous resolution [5], all persons diagnosed with chlamydia should be treated to prevent further complications and transmission. (See "Treatment of Chlamydia trachomatis infection".)

CLINICAL SYNDROMES IN FEMALES — Although the majority of females with C. trachomatis infection are asymptomatic, the pathogen is an important cause of several common clinical syndromes, discussed below.

Genitourinary tract infection — In females, the cervix is the most commonly infected anatomic site [6], and a proportion of females may also have infection of the urethra. Untreated, cervical infection can ascend into the upper genital tract to cause pelvic inflammatory disease and its sequelae of infertility and chronic pain. Pregnant women with genital chlamydial infection are also at high risk for complications. (See 'Complications of pregnancy' below.)

In addition, the presence of a cervical ectropion (namely, the presence of columnar epithelium on the outer surface of the cervix in addition to in the endocervical canal) has been epidemiologically associated with an increased risk of detection of chlamydial infection. Some investigators have reported a link between infection and subsequent risk of cervical neoplasia; the extent of this potential effect at the population level is not known [7-10].

Cervicitis — The majority (at least 85 percent) of females infected at the cervix have neither signs nor symptoms, which is the rationale for routine annual screening of young sexually active females. As an example, in a multinational study of high-risk females who were screened for genital chlamydial infection with polymerase chain reaction testing of vaginal swabs, four of five sites recorded symptoms in only 6 to 14 percent of those who developed a new infection within the first year of testing [11]. When symptoms do occur, they are highly nonspecific and can easily be confused with vaginitis or genital tract pathology: a change in vaginal discharge, intermenstrual vaginal bleeding, and post-coital bleeding. (See "Acute cervicitis".)

Similarly, abnormal exam findings are found in the minority of females with genital chlamydial infection, approximately 10 to 20 percent in some studies [12,13]. When signs are present, they include classic findings of cervicitis: mucopurulent endocervical discharge (picture 1), easily induced endocervical bleeding, or edematous ectopy (picture 2). (See "Acute cervicitis", section on 'Physical examination'.)

Dysuria-pyuria syndrome due to urethritis — Chlamydial infection of the female urethra occurs in a proportion of females with cervical infection. Screening studies of females cultured for C. trachomatis at both the cervix and urethra at sexually transmitted infection (STI) clinics suggest that approximately 50 percent have detectable organism at both sites and 25 percent from either site alone [6].

Most of these females do not report symptoms specific to the urethral tract, but some complain of typical symptoms of a urinary tract infection (UTI), such as frequency and dysuria, and may be misdiagnosed as having cystitis unless specific testing for C. trachomatis is sent [14,15]. Urinalysis reveals pyuria, but no organisms are seen on Gram stain or in bacterial culture. This combination of pyuria but no bacteriuria in sexually active females should prompt strong suspicion for chlamydial infection of the urethra.

The differential diagnosis for such a presentation includes: low-colony count UTI (eg, infection caused by Staphylococcus saprophyticus) that is not reported on culture or identified on urinalysis; or urethritis due to other STIs, such as Neisseria gonorrhoeae, Trichomonas vaginalis, or herpes simplex virus. (See "Sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults", section on 'Sterile pyuria'.)

Pelvic inflammatory disease — C. trachomatis can ascend to the upper reproductive tract (uterus, fallopian tubes, and ovaries), where pelvic inflammatory disease (PID) can result [16-20]. In some studies of females presenting to STI clinics, 2 to 4.5 percent developed clinical PID in the two weeks between diagnosis of chlamydia infection and follow-up [16-18]. One small study of 20 females with N. gonorrhoeae and C. trachomatis coinfection who were given antibiotics that were ineffective against chlamydia found a 30 percent incidence of PID after seven weeks [19]. In contrast, studies of lower risk females have found no cases of clinical PID after a year of untreated chlamydial infection [21]. These studies likely underestimate the incidence of PID in chlamydial infection, as many cases of PID may cause no symptoms and only be suspected years later in the setting of tubal infertility [22].

When symptoms of PID are present, abdominal and pelvic pain are the most common, and their presence in the setting of cervicitis or a diagnosis of chlamydial infection should prompt strong suspicion for upper genital tract involvement. Signs of PID include cervical motion and uterine or adnexal tenderness. PID due to C. trachomatis is associated with higher rates of subsequent tubal infertility, ectopic pregnancy, and chronic pelvic pain when compared with PID caused by gonorrhea, which typically causes a more acute symptomatic presentation [23,24]. The clinical manifestations, diagnosis, and treatment of PID are discussed in further detail separately. (See "Pelvic inflammatory disease: Clinical manifestations and diagnosis" and "Pelvic inflammatory disease: Treatment in adults and adolescents".)

Perihepatitis (Fitz-Hugh-Curtis syndrome) — Occasionally, patients with chlamydia infection develop perihepatitis, an inflammation of the liver capsule and adjacent peritoneal surfaces (picture 3). Perihepatitis is more commonly seen in the setting of acute PID, occurring in 5 to up to 15 percent of cases. It is associated with right-upper quadrant pain or pleuritic pain, but there are typically no liver enzyme abnormalities. The pathogenesis of this entity is not fully understood but may involve either direct extension of infected material from the cul-de-sac through the peritoneum and/or lymphatics, or an immunologically mediated mechanism. (See "Pelvic inflammatory disease: Clinical manifestations and diagnosis", section on 'Perihepatitis'.)

Complications of pregnancy — Beyond the risk of future ectopic pregnancy following chlamydia-associated PID, chlamydial genital infection during pregnancy can increase the risk for premature rupture of the membranes, preterm delivery, and low-birthweight infants [25-27]. Among 3913 pregnant Dutch women who were screened for C. trachomatis, the risk of delivery prior to 32 weeks gestation was higher in those with chlamydial infection than in those without (adjusted odds ratio 4.35, 95% CI 1.3-15.2). Miscarriage and perinatal death were not associated with chlamydial infection. The risk of transmission to the newborn is discussed elsewhere. (See "Chlamydia trachomatis infections in the newborn", section on 'Risk of transmission'.)

CLINICAL SYNDROMES IN MALES

Urogenital infection

Urethritis — C. trachomatis is the most common cause of nongonococcal urethritis in males. The proportion of cases that are asymptomatic varies by population and range from 40 to 96 percent [11,28,29]. When males do have symptoms, they typically present with a mucoid or watery urethral discharge, and dysuria is often a prominent complaint. The discharge is often clear and only seen upon milking the urethra [30]. Sometimes the discharge is so scant that males only notice stained undergarments in the morning [31]. The Gram stain of urethral discharge generally shows more than two leukocytes per high powered field (picture 4) [32], although this finding is not seen in up to a third of cases [33]. The incubation period is variable but is typically 5 to 10 days after exposure. This is in contrast to the more copious and purulent urethral discharge and shorter (two to seven days) incubation period for gonococcal urethritis. However, these syndromes frequently overlap and cannot reliably be distinguished on clinical grounds alone.

Epididymitis — C. trachomatis is one of the most frequent pathogens in epididymitis among sexually active males <35 years of age, along with N. gonorrhoeae. Males with acute epididymitis typically have unilateral testicular pain and tenderness, hydrocele, and palpable swelling of the epididymis. Occasionally, C. trachomatis infection can be misdiagnosed as a testicular malignancy [34]. Ultrasound findings include epididymal hyperemia and swelling, but a normal ultrasound does not rule out clinical epididymitis.

Asymptomatic urethritis frequently accompanies sexually transmitted epididymitis [35]. In these cases, Gram stain of urethral secretions and urine microscopy can demonstrate polymorphonuclear leukocytes.

The clinical presentation, diagnosis, and management of epididymitis are discussed in detail separately. (See "Causes of scrotal pain in children and adolescents", section on 'Epididymitis' and "Acute scrotal pain in adults", section on 'Acute epididymitis or epididymo-orchitis'.)

Prostatitis — C. trachomatis may be an etiology in some cases of chronic prostatitis, although this attribution remains highly speculative. Some studies have shown that males with chronic prostatitis without a clear bacterial etiology had detectable chlamydial antigen in urine or prostatic secretions more frequently than males with pelvic pain but no signs of prostatic inflammation (21 to 25 versus 0 to 6 percent, respectively) [36-38]. Symptoms in these males included dysuria, urinary dysfunction, pain with ejaculation, and pelvic pain. By definition, their expressed prostatic secretions demonstrated an elevated number of leukocytes on microscopy. These findings are similar to those in chronic bacterial prostatitis. (See "Chronic bacterial prostatitis".)

CLINICAL SYNDROMES COMMON TO BOTH FEMALES AND MALES

Conjunctivitis — The C. trachomatis serovars that cause genital disease (D through K) can infect the epithelial cells of the conjunctivae. This typically occurs through direct inoculation with infected genital secretions. Sexually acquired chlamydial conjunctivitis typically presents as a non-purulent erythematous injection of the epithelial surface (inclusion conjunctivitis), which may take on a cobbled appearance (picture 5).

This type of ocular infection is distinct from endemic trachoma, which is caused by serovars A through C. (See "Trachoma".)

Pharyngitis — C. trachomatis is not thought to be an important cause of pharyngitis. However, C. trachomatis has been detected in the pharynx using nucleic acid amplification testing, and some investigators postulate that this site serves as a reservoir of infection [39].

Proctitis and rectal infection — Chlamydial proctitis, defined as inflammation of the distal rectal mucosa, occurs primarily in men who have sex with men (MSM) and engage in receptive anal intercourse. Rectal infection also occurs in females, although it is much less likely to be associated with symptomatic proctitis.

Men who have sex with men – In this group, rectal C. trachomatis infection is not uncommon. In a study of over 10,000 MSM who presented to a sexually transmitted infection (STI) clinic, 14 percent tested positive for rectal C. trachomatis [40]. The clinical presentation of chlamydial proctitis depends on the infecting chlamydial serovars; in this population, infection is caused by L serovars as well as by D through K serovars [41].

L serovars – The L1, L2, and L3 serovars of C. trachomatis cause the disease known as lymphogranuloma venereum (LGV), which can present as anorectal disease and has been reported in outbreaks among European and North American MSM, particularly those with HIV [42,43]. Symptoms occur in the majority of cases. These include anorectal pain, discharge, tenesmus, rectal bleeding, and constipation, with widely varying frequencies reported in case series [42,44]. Systemic symptoms of fever and malaise are also often present. Anoscopic findings are nonspecific but include mucosal friability, internal lesions, masses or polyps, and mucopurulent exudate. The presentation can be mistaken for inflammatory bowel disease [45,46]. Left untreated, rectal infection with the L1, L2, and L3 serovars can lead to rectal fistulae and strictures. LGV is discussed in more detail elsewhere. (See "Lymphogranuloma venereum".)

D through K serovars – These non-LGV serovars, which cause genital infection, can also cause infection of the rectum, particularly in MSM. In contrast to LGV, these infections are usually asymptomatic. As an example, in a study of MSM screened for rectal chlamydial infection, only 16 percent (49 of 301 cases) of non-LGV infections were symptomatic compared with 95 percent (58 of 62 cases) of rectal LGV infections [41].

Females – Rectal C. trachomatis infection in females is typically caused by D through K serovars, is typically asymptomatic, and can occur without receptive anal intercourse. Symptomatic proctitis can also occur in females, but at a lower frequency than in MSM [47].

The burden of rectal chlamydial infection in females is likely underestimated. In one study of STI clinic attendees in Missouri who reported receptive anal intercourse, rectal infection represented 23 percent of chlamydial infections in females and would have been missed if rectal screening had not been performed; only 1 of the 66 who tested positive reported rectal discharge [48]. Rectal chlamydial infection also occurs among females who do not report receptive anal intercourse [39]. It has been reported in the majority of females (approximately 68 percent) with C. trachomatis detected on vaginal specimens [49]. In such cases, rectal infection presumably occurs through autoinoculation from infected vaginal secretions. If inadequately treated, rectal infection may place females at risk for repeat urogenital C. trachomatis infection through autoinoculation back from the anorectal site [47,50].

Genital lymphogranuloma venereum — Lymphogranuloma venereum (LGV) is primarily endemic in heterosexuals in areas of East and West Africa, India, parts of Southeast Asia, and the Caribbean and has been recognized as a sexually transmitted infection (STI) among travelers returning from those areas. The clinical manifestations of genital LGV are discussed in detail elsewhere. (See "Lymphogranuloma venereum".)

Reactive arthritis/reactive arthritis triad (RAT) — Reactive arthritis can occur following an STI. A minority of patients with sexually acquired reactive arthritis develop the complete reactive arthritis triad, with arthritis, conjunctivitis or uveitis, and urethritis or cervicitis. C. trachomatis appears to be the most common inciting pathogen for sexually acquired reactive arthritis [51,52]. In one systematic review, reactive arthritis occurred in 3 to 8 percent of people diagnosed with an STI syndrome, and most of them had proven or probable C. trachomatis infection [53]. In a subsequent study from Japan, only 1 in 123 males developed reactive arthritis following proven C. trachomatis genital infection; the authors speculated that early effective treatment of genital infection reduced likelihood of development of reactive arthritis [51].

The association between chlamydia and reactive arthritis has been further suggested by techniques that can detect chlamydial nucleic acids in synovial tissue. As an example, seven of nine patients with RAT had a positive in situ hybridization test for chlamydial RNA from samples of synovial tissue compared with 3 of 13 patients without RAT (the cause of the arthritis in these three patients was not otherwise defined) [54]. In another study, polymerase chain reaction testing detected chlamydial DNA on stored synovial tissue biopsies from five of eight patients with sexually acquired reactive arthritis and one control patient with another form of arthritis [55].

The clinical manifestations and treatment of reactive arthritis are discussed in detail separately. (See "Reactive arthritis".)

DIAGNOSIS OF CHLAMYDIAL INFECTIONS — Diagnostic techniques include nucleic acid amplification testing (NAAT), culture, antigen detection, and genetic probes; microscopy is not useful for the diagnosis of chlamydia. Because of superior sensitivity and specificity and wide availability, NAAT is the diagnostic technique of choice.

Nucleic acid amplification testing (test of choice) — Nucleic acid amplification testing (NAAT) methodology consists of amplifying C. trachomatis DNA or RNA sequences using polymerase chain reaction (PCR), transcription-mediated amplification (TMA), or strand displacement amplification (SDA). These sensitive, specific tests have become the "gold standard" and are the preferred diagnostic method, if available [35,56].

Preferred specimens for testing — The preferred testing specimen varies by syndrome:

Genitourinary infection or screening in females – Vaginal swab, which can be self-collected, is the specimen of choice. For females who are undergoing speculum exam (eg, for evaluation of symptomatic cervicitis or for routine Pap smear), NAAT can be performed on either endocervical (including cervical specimens collected into a liquid cytology medium for Pap screening) or vaginal swabs. A first-catch urine specimen is also acceptable in females but might detect up to 10 percent fewer infections when compared with vaginal and endocervical swab samples [56]. (See 'Test performance' below.)

Genitourinary infection or screening in males – First-catch urine is the specimen of choice. NAAT can also be performed on a urethral swab. For males who are unable to provide urine or prefer to collect their own swab, patient collection of a meatal swab for NAAT may be a reasonable approach. NAAT performance on self-collected meatal swabs is comparable to patient-collected urine or provider-collected urethral swabs [57-59]. However, in the United States, NAATs are not approved by the US Food and Drug Administration (FDA) for this specimen type.

Rectal infection – NAAT can be performed on a rectal swab specimen [60]. Commercially available NAATs for C. trachomatis detect both lymphogranuloma venereum (LGV) and non-LGV C. trachomatis but cannot distinguish between them. Additional molecular procedures (eg, PCR-based genotyping) can be used to differentiate LGV from non-LGV C. trachomatis, but these are not widely available [56]. Although serology is useful in the diagnosis of classic LGV, its performance in the setting of LGV proctitis is suboptimal, and it is not recommended. Clinicians who suspect LGV proctitis should seek expert advice from local public health authorities and infectious disease specialists on how to diagnose the condition effectively. Often, this is not possible, and empiric therapy is warranted. (See "Treatment of Chlamydia trachomatis infection", section on 'Proctitis and rectal infection'.)

Conjunctivitis – NAAT can be performed on conjunctival swabs to diagnose chlamydial conjunctivitis [61].

Pharyngitis – Chlamydial pharyngeal infection is thought to be uncommon and generally not a target for diagnostic testing.

Swabs should have a plastic or wire shaft and a rayon, dacron, or cytobrush tip, as other materials may be inhibitory to the organism [56].

First-catch urine submitted for NAAT should be collected from the initial stream (approximately the first 10 mL) without pre-cleansing of the genital areas. Ideally, the patient should not have voided in the two hours prior to specimen collection. The performance of these is not affected by the presence of purulent material or blood [62]. (See 'Test performance' below.)

If non-NAAT-based testing is used for diagnosis or if adequate follow-up cannot be insured, patients with signs and symptoms consistent with chlamydia should be treated empirically before diagnostic test results return. (See "Treatment of Chlamydia trachomatis infection", section on 'Indications for empiric therapy'.)

Test performance — A major advantage of NAATs is their excellent performance on specimens that can be collected without having to perform a pelvic examination in females or obtain a urethral swab in males [63]. In fact, in females, a swab of vaginal fluid is the preferred approach for diagnosing chlamydial infection, as this specimen provides the highest sensitivity [64].

A systematic review pooled data from 29 studies to assess the sensitivity and specificity of NAAT for C. trachomatis infection in urine specimens [65]. Summary estimates for sensitivity and specificity were calculated for urine and cervical sampling for three NAAT methods (PCR, TMA, or SDA). The analysis demonstrated that the sensitivity and specificity of non-invasive testing (urine) were comparable to invasive testing, although more data were available for analysis on PCR testing than the other two methods, as illustrated below:

For the 14 studies of the PCR assay, the pooled sensitivity and specificity were 83 and 99.5 percent for urine samples and 86 and 99.6 percent for cervical samples.

For the four studies of the TMA assay, the pooled sensitivity and specificity were 93 and 99 percent for urine samples and 97 and 99 percent for cervical samples.

For the two studies of the SDA assay, the pooled sensitivity and specificity were 80 and 99 percent for urine samples and 94 and 98 percent for cervical samples.

Subsequent to this meta-analysis, several studies confirmed that in females, NAAT on vaginal swab fluid, collected either by the clinician or the patient, had even higher sensitivity than urine and, in some cases, than endocervical swab [64].

Several studies have shown that NAAT on rectal specimens is more sensitive than culture in detecting rectal chlamydia and still has high specificity [63,66]. Self-collection of these samples can also provide another option to facilitate screening in men who have sex with men (MSM) [67].

Other diagnostic techniques

Rapid tests for chlamydia — Although NAAT has replaced culture as the new "gold standard," same-day results have traditionally not been available. Rapid NAAT-based tests have been developed. As they become more available, the circumstances and settings in which they should be used will likely depend on practical issues, such as waivers for non-laboratory use and cost [68].

The XPert C. trachomatis/N. gonorrhoeae (CT/NG) assay is an NAAT that can provide testing results for chlamydia (and gonorrhea) within 90 minutes [69]. This test is FDA approved for use on endocervical or vaginal swabs and urine. Another CT/NG NAAT assay (binx io) uses electrochemical detection technology to provide results in approximately 30 minutes [70]. It is FDA approved for use on vaginal swabs. The sensitivity, specificity, positive predictive value, and negative predictive value for CT were 96, 99, 91, and 100 percent, respectively.

Tests not routinely recommended

Culture – Culture methods are now limited to research and reference laboratories due to the expense and technical expertise required.

SerologyC. trachomatis serology (complement fixation titers >1:64) can support the diagnosis of chlamydia in the appropriate clinical context but is performed infrequently, not standardized, and requires a high level of expertise to interpret. It may also not perform as well in diagnosing rectal infections in males as it does in upper genital tract infection in females.

Antigen detection – Antigen detection requires invasive testing using a swab from the cervix or urethra. The sensitivity of this method is 80 to 95 percent compared with culture.

Genetic probe methods – Because they do not involve amplification of genetic targets, available genetic probe methods require invasive testing using a direct swab from the cervix or urethra. The sensitivity of this assay is approximately 80 percent compared with culture. The main advantage of these tests is their low cost; however, because their sensitivity is considerably lower than NAAT and because NAAT have become more cost-competitive, these tests are not used as frequently as in the past.

Whom to test

Symptomatic and at-risk asymptomatic patients — Any sexually active individual with signs and symptoms consistent with the clinical syndromes associated with chlamydia should undergo diagnostic testing for C. trachomatis. However, because the majority of chlamydial infections are asymptomatic, routine screening with NAAT should be offered to sexually active patients at high risk of infection and complications of chlamydia [35,71]. Details on whom to screen for chlamydia are discussed in detail elsewhere (table 1). (See "Screening for sexually transmitted infections", section on 'Screening recommendations'.)

Furthermore, any patients with documented gonococcal infection should also undergo testing for chlamydia.

Finally, any patient who has been treated for chlamydia should be rescreened approximately three months after treatment, regardless of whether they believe their sex partners were treated [35]. High rates of reinfection have been documented in the months after an initial chlamydial infection [72,73]. (See "Treatment of Chlamydia trachomatis infection", section on 'Retesting for all patients'.)

Patients with recent exposure — In patients who present within one to two weeks of a potential or known exposure to chlamydia (eg, sexual assault), diagnostic testing should not be used to inform the decision to treat. Such patients should be treated empirically. (See "Treatment of Chlamydia trachomatis infection", section on 'Management of sex partners'.)

Patients with persistent symptoms — Persistent symptoms in patients with confirmed chlamydial infection after appropriate therapy with good adherence are usually not due to primary treatment failure. In a longitudinal cohort of adolescent females assessed every three months, NAAT testing and ompA genotyping were used to characterize rates of reinfection or persistent infection using molecular description [74]. The investigators observed 478 episodes of infection in 210 participants. Of these females, 121 had repeat infections. Most of these (84 percent) were likely reinfections, 14 percent were classified as probable or possible treatment failures, and only 2.2 percent were infections that persisted in the absence of documented treatment.

Thus, persistent symptoms related to chlamydial infection are usually due to recurrent infections. Clinicians should inquire about possible reinfection, including whether sex partners were treated. NAAT remains the test of choice to evaluate for reinfection in the setting of persistent symptoms, regardless of interval since the prior treatment.

Recurrence of symptoms — Recurrence of symptoms after initial resolution should lead to a repeat evaluation for chlamydia and other sexually transmitted diseases that cause urethritis or cervicitis, including gonorrhea, bacterial vaginosis, and other pathogens. NAAT remains the test of choice to evaluate for reinfection in the setting of symptom recurrence, regardless of interval since the prior treatment. A repeat diagnosis of chlamydia in a previously treated patient usually indicates reinfection, as noted above.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of chlamydia depends on the particular clinical syndrome. These are discussed separately:

(See "Acute cervicitis", section on 'Epidemiology and etiology'.)

(See "Pelvic inflammatory disease: Pathogenesis, microbiology, and risk factors", section on 'Microbiology'.)

(See "Urethritis in adult males", section on 'Epidemiology and microbiology' and "Urethritis in adult males", section on 'Differential diagnosis'.)

(See "Acute scrotal pain in adults".)

(See "Conjunctivitis", section on 'Classification and epidemiology'.)

(See "Evaluation of acute pharyngitis in adults", section on 'HIV and other sexually transmitted infections'.)

(See "Evaluation of anorectal symptoms in men who have sex with men", section on 'Proctitis'.)

Any testing for C. trachomatis should also prompt testing for N. gonorrhoeae. N. gonorrhoeae not only causes similar clinical syndromes as C. trachomatis but also coexists in a significant proportion of patients with chlamydial infection. (See "Treatment of Chlamydia trachomatis infection", section on 'Evaluate for and treat gonococcal coinfection'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sexually transmitted infections".)

SUMMARY AND RECOMMENDATIONS

Clinical syndromes in females In females, Chlamydia trachomatis most commonly affects the cervix. The majority of infected females are asymptomatic, although some may present with the typical findings of cervicitis, including vaginal discharge, abnormal vaginal bleeding, and purulent endocervical discharge on exam. Concurrent rectal infection is detected in around two-thirds of women infected with urogenital chlamydia. (See 'Cervicitis' above.)

The most concerning complication of untreated cervical chlamydial infection is pelvic inflammatory disease, which in turn can lead to infertility, ectopic pregnancy, or chronic pelvic pain. (See 'Pelvic inflammatory disease' above and "Pelvic inflammatory disease: Clinical manifestations and diagnosis", section on 'Clinical features'.)

Clinical syndromes in males – In males, C. trachomatis is a common cause of nongonococcal urethritis. The majority of infected males are asymptomatic. When present, symptoms include a mucoid or watery urethral discharge and dysuria. C. trachomatis is a frequent cause of acute epididymitis in males younger than 35 years of age and may be an etiology in some cases of chronic prostatitis. (See 'Urogenital infection' above.)

The serovars of C. trachomatis that cause lymphogranuloma venereum have been increasingly reported in cases of proctitis in men who have sex with men. These cases tend to be symptomatic, with anorectal pain, discharge, and tenesmus, and can be mistaken for inflammatory bowel disease. (See 'Proctitis and rectal infection' above.)

Diagnostic testing The diagnostic test of choice for chlamydial infection of the genitourinary tract is nucleic acid amplification testing (NAAT) of vaginal swabs for females or urine for males. NAAT should also be used on rectal swabs to diagnose chlamydial proctitis. If non-NAAT-based testing is used for diagnosis or if adequate follow-up cannot be insured, patients with signs and symptoms consistent with chlamydia should be treated empirically before diagnostic test results return. (See 'Diagnosis of chlamydial infections' above.)

Whom to test – Any sexually active individual with signs and symptoms consistent with the clinical syndromes associated with chlamydia and patients with documented gonococcal infection should undergo diagnostic testing for C. trachomatis. Because the majority of chlamydial infections are asymptomatic, routine screening with NAAT should be offered to sexually active patients at high risk of infection and complications of chlamydia. (See 'Whom to test' above and "Screening for sexually transmitted infections", section on 'Screening recommendations'.)

Testing for gonorrheaNeisseria gonorrhoeae not only causes similar clinical syndromes as C. trachomatis but also coexists in a significant proportion of patients with chlamydial infection. Thus, any testing for C. trachomatis should also prompt testing for N. gonorrhoeae. (See 'Differential diagnosis' above and "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents", section on 'Diagnostic approach'.)

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