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Chlamydia trachomatis is the most common bacterial cause of sexually

transmitted genital infections


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.
CLINICAL SYNDROMES IN WOMEN
Genital infection In women, the cervix is the most commonly infected
anatomic site [ 2 ], and a proportion of women may also have infection of the
urethra. Untreated, cervical infection can ascend 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.
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.
The incubation period of symptomatic disease generally ranges from 7 to 14
days following infection.
Dysuria-pyuria syndrome due to urethritis
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.
This combination of pyuria but no bacteriuria in a young, sexually active woman
should prompt strong suspicion for chlamydial infection of the urethra.
differential diagnosis for such a presentation includes low-colony count urinary
tract infection (eg, infection caused by Staphylococcus saprophyticus), or
urethritis due to other sexually transmitted disease organisms, such as N.
gonorrhoeae or herpes simplex virus.
Pelvic inflammatory disease

C. trachomatis can ascend to the upper reproductive tract, where pelvic


inflammatory disease (PID) can result
2 to 4.5 percent developed clinical PID in the two weeks between diagnosis of
chlamydia infection and follow-up
lower risk women have found no cases of clinical PID after a year of untreated
chlamydial infection
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
When symptoms of PID are present, abdominal or 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
Perihepatitis (Fitzhugh-Curtis syndrome)
Occasionally, patients with chlamydia infection develop perihepatitis, an
inflammation of the liver capsule and adjacent peritoneal surfaces ( picture 3 ).
in the setting of actual 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.
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 and preterm delivery
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 OR 4.35, 95% CI 1.3-15.2).
Miscarriage and perinatal death were not associated with chlamydial infection.
Proctitis

While women can experience rectal infection with chlamydia, the responsible
strains are the typical genital serovars (D through K), and they are typically
asymptomatic and do not have long-term sequelae. This is in contrast to the
proctitis caused by the LGV serovars (L1, L2, L3), which almost exclusively
affect men who have sex with men.

CLINICAL SYNDROMES IN MEN


Urogenital infection

Urethritis

most common cause of nongonococcal urethritis in men


asymptomatic vary by population and range from 40 to 96 percent
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
The Gram stain of urethral discharge generally shows more than five leukocytes
per high powered field ( picture 4 ), although this finding is not seen in up to a
third of cases
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 only.

Epididymitis
C. trachomatis is one of the most frequent pathogens in epididymitis among
sexually active men <35 years of age, along with Neisseria 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 [ 22 ]. Ultrasound
findings include epididymal hyperemia and swelling, but a normal ultrasound
does not rule out clinical epididymitis.
Asymptomatic urethritis frequently accompanies sexually transmitted
epididymitis
Gram stain of urethral secretions and urine microscopy can demonstrate
polymorphonuclear leukocytes
Prostatitis
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)
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.
Proctitis
Chlamydial proctitis, defined as inflammation of the distal rectal mucosa, is
relatively uncommon and occurs almost exclusively in men who have sex with
men (MSM) who have had receptive anal intercourse
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
These include anorectal pain, discharge, tenesmus, rectal bleeding and
constipation, with widely variant frequencies reported in case series

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 [ 29,30 ].
Left untreated, rectal infection with the L1, L2, and L3 serovars can lead to
rectal fistulae and strictures.
Reactive arthritis/reactive arthritis triad (RAT)
Approximately 1 percent of men with urethritis develop reactive arthritis, and
approximately one-third of these patients have the complete reactive arthritis
triad (RAT) formerly referred to as Reiter syndrome (arthritis, uveitis, and
urethritis).
C. trachomatis appears to be the most common inciting pathogen
suggested by techniques that can detect chlamydial nucleic acids in synovial
tissue.
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 conjunctiva. 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.
Pharyngitis C. trachomatis is not thought to be an important cause of
pharyngitis.
Genital lymphogranuloma venereum
these cases generally run a benign course with finding of a non-painful, small,
stellate genital ulcer followed by development of inguinal lymphadenopathy
(buboes).

DIAGNOSIS OF CHLAMYDIAL INFECTIONS

genitourinary tract is nucleic acid amplification testing (NAAT) of vaginal swabs


for women or first-catch urine for men, although NAAT can also be performed
on endocervical and urethral swab specimens
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.
Rectal chlamydial infection in persons who engage in receptive anal intercourse
can be diagnosed by testing a rectal swab specimen.
NAAT can be performed on conjunctival swabs to diagnose chlamydial
conjunctivitis. Chlamydial pharyngeal infection is thought to be uncommon and
generally not a target for diagnostic testing.
Diagnostic techniques
Diagnostic techniques include NAAT, culture, antigen detection, and genetic
probes; microscopy is not useful for the diagnosis of chlamydia.
noninvasive screening options, such as first-catch urine testing or self-collected
vaginal swabs, are possible and have become the diagnostic approach of choice
for chlamydial (and gonococcal) infections. However, for women presenting with
symptomatic cervicitis who undergo a speculum exam, or for high-risk women
undergoing routine Pap smear, NAAT can be performed on either endocervical or
vaginal swabs.
Nucleic acid amplification 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 and specific tests have become the "gold standard", and
are the preferred diagnostic method, if available.
Rapid tests for Chlamydia
Several immunoassay-based tests are being developed, which are based on
monoclonal antibody binding of chlamydial antigens from self-collected samples.
These rapid tests provide results within 30 minutes of testing and are less

expensive to perform and simple to interpret since testing results are reflected
in a test strip color change
Chlamydia Rapid Test (CRT) on first-void urine in men
This assay, based on use of a monoclonal antibody to chlamydia
lipopolysaccharide, was compared to NAAT (PCR) as a gold standard.
Culture
Serology C. trachomatis serology (complement fixation titers >1:64) can
support the
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
Patients with recent exposure
Patients with persistent symptoms
Recurrence of symptoms

DIFFERENTIAL DIAGNOSIS

Urogenital infection
Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium, can
cause infections similar to C. trachomatis.

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

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

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

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 "Clinical features and diagnosis of pelvic
inflammatory disease", section on 'Clinical features' .)

In men, Chlamydia trachomatis is the most common cause of


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

The serovars of Chlamydia 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. Many laboratories have also validated NAAT 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
Chlamydia 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 Chlamydia trachomatis" .)

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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