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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

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan 2020. | This topic last updated: Oct 21, 2019.

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 men and women 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
men and women.

The clinical manifestations and diagnosis of C. trachomatis in women and men 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 men than in women (mean untreated infection
duration of 2.84 and 1.35 years in men and women, 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 WOMEN

Although the majority of women with C. trachomatis infection are asymptomatic, the pathogen is an
important cause of several common clinical syndromes, discussed below.

Genitourinary tract infection — In women, the cervix is the most commonly infected anatomic
site [6], and a proportion of women 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 women infected at the cervix have neither
signs nor symptoms, which is the rationale for routine annual screening of young sexually active
women. As an example, in a multinational study of high-risk women 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 women 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 women with cervical infection. Screening studies of women 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 women 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 women 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 women 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
women 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 women 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 [25,26]. 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'.)

Proctitis — Anal intercourse is not uncommon among heterosexuals, and women can also have
rectal infection with chlamydia [27,28]. The clinical presentation of chlamydial rectal infection
depends on the infecting serovars. In women, the responsible strains are the genital serovars D
through K, and they are typically asymptomatic and do not have long-term sequelae at this site.
This is in contrast to the proctitis caused by the lymphogranuloma venereum serovars (L1, L2, L3),
which almost exclusively affect men who have sex with men. Nevertheless, symptomatic proctitis
has also been reported in women [29]. (See 'Proctitis' below.)

The burden of chlamydial rectal infection in women is likely underestimated. In one study of STI
clinic attendees in Missouri who reported receptive anal intercourse, rectal infection represented
23 percent of chlamydia infections in women and would have been missed if rectal screening had
not been performed [30]. Of the 66 women who tested positive at the rectal site, only one reported
rectal discharge. Furthermore, a significant number of women who test positive for rectal
chlamydial infection do not report receptive intercourse [31].

Many questions remain about the significance of positive rectal chlamydia testing in women. Its
role in persistent infection or ongoing transmission, despite or because it is typically asymptomatic,
is unclear.

CLINICAL SYNDROMES IN MEN

Urogenital infection

Urethritis — C. trachomatis is the most common cause of nongonococcal urethritis in men. The
proportion of cases that are asymptomatic varies by population and range from 40 to 96 percent
[11,32,33]. When men 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 [34]. Sometimes the discharge is so scant that men only notice stained
undergarments in the morning [35]. The Gram stain of urethral discharge generally shows more
than two leukocytes per high powered field (picture 4) [36], although this finding is not seen in up to
a third of cases [37]. 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 men <35 years of age, along with N. gonorrhoeae. Men 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
[38]. Ultrasound findings include epididymal hyperemia and swelling, but a normal ultrasound does
not rule out clinical epididymitis.

Asymptomatic urethritis frequently accompanies sexually transmitted epididymitis [39]. 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
"Evaluation of 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 men with chronic
prostatitis without a clear bacterial etiology had detectable chlamydial antigen in urine or prostatic
secretions more frequently than men with pelvic pain but no signs of prostatic inflammation (21 to
25 versus 0 to 6 percent, respectively) [40-42]. Symptoms in these men 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".)

Proctitis — Chlamydial proctitis, defined as inflammation of the distal rectal mucosa, occurs
primarily in men who have sex with men (MSM) who engage in receptive anal intercourse. In this
group, infection is not uncommon and can be caused by D through K and L serovars [43]. 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 [44]. The clinical presentation of chlamydial
proctitis depends on the infecting chlamydial 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 who are HIV infected [45,46].
Symptoms occur in the majority of cases. These include anorectal pain, discharge, tenesmus,
rectal bleeding, and constipation, with widely variant frequencies reported in case series [45,47].
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 [48,49]. Left untreated,
rectal infection with the L1, L2, and L3 serovars can lead to rectal fistulae and strictures. (See
"Lymphogranuloma venereum".)

The non-LGV serovars that cause genital infection (serovars D through K) can also cause infection
of the rectum, particularly in MSM, but in contrast to LGV, these infections are usually
asymptomatic. As an example, in a study that screened MSM for rectal chlamydial infection, only
49 of 301 cases (16 percent) of non-LGV infection were symptomatic compared with 58 of 62
cases (95 percent) of rectal LGV infection [43]. Routine annual screening of this site (or more
frequently, in those at ongoing risk) is recommended for MSM, particularly in the HIV-infected
person [32,39].

CLINICAL SYNDROMES COMMON TO WOMEN AND MEN

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). (See "Conjunctivitis", section on 'Adult inclusion conjunctivitis'.)

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 [31].

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 [50,51]. In one
systematic review, reactive arthritis occurred in 3 to 8 percent of men and women diagnosed with
an STI syndrome, and most of them had proven or probable C. trachomatis infection [52]. 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 [50].

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) [53]. 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 [54].

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.

If NAAT methods are unavailable, antigen detection and genetic probe methods can be applied to
endocervical or urethral swabs to diagnose chlamydia. In resource-limited settings, rapid tests for
chlamydia may be used for diagnosis, if available. When no specific diagnostic tests are available,
the presumptive diagnosis of chlamydia is made when symptoms and signs of the clinical
syndromes associated with chlamydia are present in young or sexually active patients.

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 [39,55].

Preferred specimens for testing — The preferred testing specimen varies by syndrome:
 ● Genitourinary infection or screening in women – Vaginal swab, which can be self-collected, is
the specimen of choice. For women 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 women but
might detect up to 10 percent fewer infections when compared with vaginal and endocervical
swab samples [55]. (See 'Test performance' below.)

● Genitourinary infection or screening in men – First-catch urine is the specimen of choice.

NAAT can also be performed on a urethral swab.

● Rectal infection – NAAT can be performed on a rectal swab specimen [56]. 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 [55]. 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'.)

● Conjunctivitis – NAAT can be performed on conjunctival swabs to diagnose chlamydial

conjunctivitis [57].

● 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 [55].

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 [58]. (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 women or obtain a urethral
swab in men [59]. In fact, in women, a swab of vaginal fluid is the preferred approach for
diagnosing chlamydial infection, as this specimen provides the highest sensitivity [60].

A systematic review pooled data from 29 studies to assess the sensitivity and specificity of NAAT
for C. trachomatis infection in urine specimens [61]. 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 women, 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 [60].

Several studies have shown that NAAT on rectal specimens is more sensitive than culture in
detecting rectal chlamydia and still has high specificity [59,62]. Self-collection of these samples can
also provide another option to facilitate screening in men who have sex with men (MSM) [63].

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
[64].

The XPert C. trachomatis/N. gonorrhoeae (CT/NG) assay is an NAAT that can provide testing
results for chlamydia (and gonorrhea) within 90 minutes [65]. This test is US Food and Drug
Administration (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 [66]. 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.

● Serology – C. 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 men as it does in upper genital tract infection in women.

● 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 [39,67]. This includes women who are 24 years old
or younger, pregnant, or have new or many sexual partners, as well as MSM and sexually active
HIV-infected individuals of any age. In addition, consideration should be given to routine annual
screening in sexually active persons with HIV, regardless of age. Persons who engage in receptive
anal intercourse, particularly MSM, warrant screening at both urogenital and rectal sites. Screening
of at-risk patients is discussed elsewhere. (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 [39].
High rates of reinfection have been documented in the months after an initial chlamydial infection
[68,69]. (See "Treatment of Chlamydia trachomatis infection", section on 'Retesting'.)

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 women assessed every three months,
NAAT testing and ompA genotyping were used to characterize rates of reinfection or persistent
infection using molecular description [70]. The investigators observed 478 episodes of infection in
210 participants. Of these women, 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

Urogenital infection — Other sexually transmitted pathogens, including N. gonorrhoeae,

Trichomonas vaginalis, and Mycoplasma genitalium, can cause infections similar to C. trachomatis.
The differential diagnosis of urogenital chlamydial infections depends on the particular clinical
syndrome and is discussed in separate topic reviews. (See "Acute cervicitis", section on
'Epidemiology and etiology' and "Pelvic inflammatory disease: Clinical manifestations and
diagnosis", section on 'Differential diagnosis' and "Urethritis in adult men", section on
'Nongonococcal urethritis' and "Urethritis in adult men", section on 'Differential diagnosis'.)

Proctitis — The differential diagnosis of infectious proctitis in men who have sex with men (MSM)
also includes N. gonorrhoeae, herpes simplex virus, and Treponema pallidum infections [71]. The
frequency of these causes was evaluated in a review of 101 episodes of proctitis among MSM in
San Francisco; anoscopy was performed and specimens obtained that were tested for the above
organisms [71]. The following frequency of causes was noted:

● None – 45 percent
● Gonorrhea only – 20 percent
● Herpes simplex only – 13 percent
● Chlamydia only – 11 percent
● Mixed infections – 10 percent, including 8 percent with chlamydia
● Syphilis only – 1 percent

The addition of molecular testing for M. genitalium and T. vaginalis in a subsequent cohort of MSM
in San Francisco did not appear to reduce the proportion of clinical proctitis cases of unknown
etiology [72].

Coinfection with N. gonorrhoeae — It is important to note that N. 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 "Treatment of Chlamydia trachomatis infection", section on 'Coinfection with
gonorrhea'.)
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

● In women, Chlamydia trachomatis most commonly affects the cervix. The majority of infected
women are asymptomatic, although some may present with the typical findings of cervicitis,
including vaginal discharge, abnormal vaginal bleeding, and purulent endocervical discharge
on exam. (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'.)

● In men, C. trachomatis is a common cause of nongonococcal urethritis. The majority of

infected men are asymptomatic. When present, symptoms include a mucoid or watery urethral
discharge and dysuria. C. trachomatis is a frequent cause of acute epididymitis in men
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' above.)

● The diagnostic test of choice for chlamydial infection of the genitourinary tract is nucleic acid
amplification testing (NAAT) of vaginal swabs for women or urine for men. 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.)

● 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'.)

● Neisseria 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.)

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Topic 83019 Version 30.0

GRAPHICS

Chlamydia cervicitis

Mucopurulent discharge is visible coming from the os in a patient with

Chlamydia cervicitis. The cervix is erythematous and friable.

Reproduced from the Centers for Disease Control and Prevention.

Graphic 67848 Version 2.0

Edematous ectopy

Courtesy of Seattle STD/HIV Prevention Training Center (Claire Stevens,

photographer).

Graphic 84032 Version 1.0

Perihepatitis in chlamydia infection

Inflammation of the liver capsule and adjacent peritoneum can be seen via
laparascope as an uncommon finding in women with Chlamydial infection.

Reproduced from the Centers for Disease Control and Prevention.

Graphic 50868 Version 2.0

Gram stain of urethral discharge

Polymorphonuclear leukocytes without intracellular pathogens are

characteristic of the mucopurulent discharge seen in men with chlamydial
infection.

Reproduced from the Centers for Disease Control and Prevention.

Graphic 56547 Version 2.0

Chlamydia conjunctivitis

Courtesy of the Seattle STD/HIV Prevention Training Center.

Graphic 84033 Version 1.0

Contributor Disclosures
Katherine Hsu, MD, MPH, FAAP Nothing to disclose Jeanne Marrazzo, MD, MPH, FACP,
FIDSA Grant/Research/Clinical Trial Support: BD Diagnostics [Vaginal infections, STI (diagnostic tests)].
Consultant/Advisory Boards: BD Diagnostics [Vaginitis (diagnostic testing strategies)]; Gilead [HIV (pre-exposure
prophylaxis)]. Other Financial Interest: Gilead [HIV (Data and Safety Monitoring Board member)]. Allyson
Bloom, MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
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