Introduction

The spectrum of genital infections caused by serotypes of C trachomatis has only recently become
appreciated. Chlamydia (from Greek, χλαμύδα meaning "cloak") infections are the most commonly
reported notifiable disease in in industrialized countries. In 2004, 929,462 chlamydia infections were
reported to the CDC, which is 2.5 times greater than the number of cases of gonorrhea. As many as 10
percent of women of childbearing age are infected in inner cities in the UK. Women under 25 years of
age have the highest prevalence. Genital infection with this organism is the most common sexually
transmitted bacterial disease in women.

Certain factors may be predictive of women with a greater likelihood of acquiring C trachomatis.
Sexually active women younger than 20 years have chlamydial infection rates 2–3 times higher than
the rates of older women. The number of sexual partners and, in some studies, lower socioeconomic
status are associated with higher chlamydial infection rates. Persons who use barrier contraception are
less frequently infected by C trachomatis than are those who use no contraception, and women who
use oral contraceptives may have a higher incidence of cervical infection than women not using oral
contraceptives. Cervical infection in pregnant women varies from 2–24% and is most prevalent in
young, unmarried women of lower socioeconomic status in inner-city environments. The CDC
recommends screening sexually active adolescent girls at their routine yearly gynecologic examination,
as well as women 20–24 years old, especially those who have new or multiple partners, and those who
inconsistently use barrier contraceptives.

Pathogenesis

Chlamydiae are small (250-1000 nm) obligate intracellular microorganisms that have a cell wall similar
to that of gram-negative bacteria. They belong to family Chlamydiaceae and class Chlamydia They are
classified as bacteria and contain both DNA and RNA. There are 4 different types of Chlamydia: C.
trachomatis (agent of urogenital chlamydia, trachoma, Lymphogranuloma venereum), C. psittaci
(causes SARS arthritis, pyelonephritis), C. pneumoniae (pathogen ARD, pneumonia), C. resogit (role in
the pathogenesis of humans is not known). They divide by binary fission, but like viruses they grow
intracellularly. They can be grown only by tissue culture. It has a unique developmental cycle, includes
two forms of existence: the elementary bodies (infectious form adapted for extracellular survival) and
reticular cells (vegetative form, which provides intracellular multiplication). Elementary bodies of
phagocytes of the host organism, but it is not digested (incomplete phagocytosis), and transformed
into reticular cells and actively proliferate. Developmental cycle of chlamydia is 48-72 h and ends with
the rupture of the host cell and yield of elementary bodies in intercellular space. 
Chlamydia is unstable in the environment, it is easy to die when exposed to antiseptics, ultraviolet
light, boiling, drying. Infection occurs mainly through sexual contact with an infected partner,
transplacentally and intrapartum, rarely through household way via toiletries, laundry, and bed.

With the exception of the L serotypes, chlamydiae attach only to columnar epithelial cells without deep
tissue invasion. As a result of this characteristic, clinical infection may not be apparent. For example,
infections of the eye, respiratory tract, or genital tract are accompanied by discharge, swelling,
erythema, and pain localized to these areas only.

C. trachomatis infections are associated with many adverse sequelae due to chronic inflammatory
changes as well as fibrosis (eg, tubal infertility and ectopic pregnancy). Serovars A-C cause trachoma,
infecting the conjunctiva. Serovars D-K cause genital infections. Specific LGV serovars (Ll-L3) cause LGV.
They gain entry to the cells by binding to specific surface receptors. Once inside the cell, inclusion
bodies form, which contain the metabolically active reticulate bodies. These divide by binary fission.
After a 48-hour life cycle, reticulate bodies condense into elementary bodies which are released from
the cell surface. Heavily infected cells die but it is the inflammatory response to infection that
contributes most to damaging the epithelial surface. The proposed mechanism for the pathogenesis of
chlamydial disease is an immune-mediated response. This mechanism has been supported C.
trachomatis vaccine studies in humans and monkeys as well as other animal model studies. Evidence
indicates that a 57-kDa chlamydial protein, which is a member of 60-kDa heat shock proteins, plays a
role in the immunopathogenesis of chlamydial disease. Humoral immunity may protect from re-
infection, but antibodies are serovar specific and the protection is short lived. Cell-mediated immunity,
with activation of cytotoxic T cells and production of interferon-gamma, is more important for
controlling established infection.

Classification 

A widely accepted clinical classification does not exist.  Clinically, it maybe divided into acute (disease
duration up to 2 months), chronic (disease is more than 2 months); and carrier state of schlamydial
infection. In addition, the disease is divided based on location into uncomplicated chlamydia of the
lower urogenital system, upper urogenital syatem and pelvic organs, and chlamydia at other sites. 

Clinical Findings

Symptoms and Signs

Women with chlamydial infection not uncommonly are asymptomatic: approximately 50 per cent
in men and 80 per cent in women. In men it is the most important cause of NGD. In women it causes
cervicitis and PID. Women with cervical infection generally have a
mucopurulent discharge with hypertrophic cervical inflammation.
Genital strains can colonize the throat and also cause conjunctivitis.
It can infect the rectum, although only lymphogranuloma venereum
(LGV) strains of Chlamydia cause a severe proctitis.

Salpingitis may be unassociated

with symptoms. Suspected
chlamydial infection may cause Figure 1 Chlamydial cervicitis in a female
patient characterized by mucopurulent
junction adhesions between the cervical discharge, erythema, and
liver and the parietal inflammation.
peritoneum (perihepatitis), also
known as syndrome of Fitz-Hugh-Curtis. It is usually detected
Figure 2 Conjunctivitis due to chlamydia. during laparoscopy or laparotomy. Due to scarce and/or non-
specific symptoms, disease is impossible to identify based on
clinical signs and symptoms. Diagnosis of Chlamydia trachomatis is based only on the results of
laboratory studies. 

Essentials of Diagnosis

 Mucopurulent cervicitis.
 Salpingitis.
 Urethral syndrome.
 Nongonococcal urethritis in males.
 Neonatal infections.
 Lymphogranuloma venereum.

Laboratory Findings

The diagnosis of chlamydial infection is based solely on laboratory

Figure 3 Pap smear showing C. trachomatis
(H&E stain)
tests. Diagnosis of C trachomatis using cell culture isolation has a
sensitivity of 70–90%; however, this specialized modality is not
widely available. Cell culture is the detection method of greatest
specificity (almost 100%), but the cost can be prohibitive, and a 3-
to 7-day delay in diagnosis is required. Despite its disadvantages,
cell culture is presently the standard for quality assurance of non-
culture chlamydia tests and it is the "Gold standard" for detection
of intracellular parasites. The CDC recommends cell culture for
specimens from the urethra, rectum, and vagina of prepubertal
girls and from the nasopharynx of infants so that columnar epithelial cells are harvested. In infants with
inclusion conjunctivitis, Giemsa stain of purulent discharge from the eye is used to identify chlamydial
inclusions, but similarly stained slides of exudates in adults with genital infections are only
approximately 40% accurate in the diagnosis of these infections.

Serologic methods, either the complement fixation or microimmunofluorescence test, are not totally
accurate, as 20–40% of sexually active women have positive antibody titers. In fact, most women with
microimmunofluorescent antibody do not have a current infection.

In order to clarify the diagnosis and determine the phase of the

disease we can identify chlamydial antibodies classes A, M, G in the
serum. In the acute phase of chlamydial infection, the titer of IgM
increases, the transition to a chronic phase causes the increase of IgA
titers, and then IgG. Reduced titers of chlamydial antibody classes A, G
in the treatment process is an indication of treatment positive effects. 
Diagnosis of urogenital Chlamydia trachomatis by detection of Figure 4 Chlamydia trachomatis
inclusion bodies (brown) in a McCoy
antibodies IgA, IgM, IgG is not recommended by global and national cell culture.
guidelines. Moss and colleagues examined antibody responses to
chlamydia species in patients who attended a genitourinary clinic and found that up to 50% of all
chlamydia IgG-positive cases were due to nongenital chlamydiae (C pneumoniae and C psittaci). The
low specificity of the chlamydia serology tests is attributed to these antibodies as well as to the
presence of group-specific antibodies. Therefore, it is of utmost importance to use serologic tests
capable of distinguishing antibodies to C trachomatis from antibodies to C pneumoniae and C psittaci
(nongenital chlamydial pathogens). Direct smear fluorescent antibody testing or direct fluorescent
antibody (DFA) test requires a fluorescence microscope, and processing time is only 30–40 minutes.
Sensitivity is 90% or higher, with a specificity of 98% or higher if an experienced microscopist and a
satisfactory specimen are available. This test appears to be the most promising, and when tissue
samples (endometrial or uterine tube) are being evaluated, it has been reported to be more accurate.
ELISA tests cannot be used reliably on rectal or conjunctival swabs, for which DFA is more appropriate.

PCR, ligase chain reaction, and current DNA probes used for detection of C trachomatis may be more
rapid and less expensive. They can be applied to urine samples or vaginal swabs and have detection
rates superior to ELISA tests on cervical swabs. This means that non-invasive screening for Chlamydia is
now possible. Unfortunately, higher cost has limited the availability of such tests in the UK. Nucleic acid
hybridization methods (DNA probe) require only 2–3 hours of processing time. The DNA probe assay is
specific for C trachomatis; cross-reactivity with C pneumoniae and C psittaci has not been reported. To
ensure high specificity, a competitive probe assay has been produced and is currently being evaluated
in clinical trials. Recent reports indicate PCR positivity with negative culture. PCR may be the most
sensitive and specific test method for chlamydia.
Table 1 Interpreting the results of serological examination for Chlamydia

 Stage of disease IgM IgA IgG

Acute chlamydia (2 weeks from onset) + - -
Acute chlamydia (2,5 - 3 weeks from onset) + + -
Acute chlamydia (3-4 weeks from onset) + + +
Exacerbation of long course of chlamydia (2
+ + +
weeks from onset)
Duration of the current chlamydia - +/- +/-
Past (after) infection - - +
reduce titer by 2-4 reduce titer by 4-8 times
Recovery - times after successful over 1-1.5 months after
treatment successful treatment
In negative result - - -

The only situation where a serological blood test for chlamydia has no practical application is in tubal
infertility in women. In the presence of the triad:

 The presence of antibodies class G to C. trachomatis

 Established by instrumental methods fact tubal infertility
 Elevated levels of C-reactive protein (CRP) in blood plasma,

anti-chlamydial treatment is initiated, but the diagnosis of urogenital Chlamydia trachomatis is not
confimed.

Table 2 Laboratory investigations and their pros and cons

Method Microscopy * Antigen - ELISA PCR

Sensitivity 74% -90% 71% -97% 90%
Specificity 98% -99% 97% -99% 99% -100%
Benefits Fast and cheap fast sensitive
Shortcomings subjective expensive, require expensive
special equipment
* Using a fluorescence microscope for direct immunofluorescence reaction or DFA (direct immunofluorescence assay)

In Scandinavian countries, nationwide screening programmes have reduced the incidence of

chlamydial infection, with concomitant reductions in the incidence of PID and ectopic pregnancy. A
national screening programme is starting in the UK. Serological tests are not performed routinely in the
diagnosis of chlamydial infections. Micro-immunofluorescence can be used to detect serum antibodies,
which are not present in all infected individuals. The highest antibody titres are found in women with
PID or disseminated infection. These highest titres are present in 60 per cent of women with tubal
factor infertility.
Differential Diagnosis

Mucopurulent cervicitis is frequently caused by N. gonorrhoeae, and selective cultures for this
organism should be performed. As discussed above, C. trachomatis alone may be associated with as
many as 20–35% of cases of acute salpingitis in the United States. In both cervicitis and salpingitis,
cultures frequently may be positive for both organisms.

Complications

Adverse sequelae of salpingitis, specifically infertility due to tubal obstruction and ectopic pregnancy,
are the most direct complications of these infections. Pregnant women with cervical chlamydial
infection can transmit infections to their newborns; evidence indicates that up to 50% of infants born
to such mothers will have inclusion conjunctivitis. In perhaps 10% of infants, an indolent chlamydial
pneumonitis develops at 2–3 months of age. This pathogen may cause otitis media in the neonate.
Whether maternal cervical infection with Chlamydia causes significantly increased fetal and perinatal
wastage by abortion, premature delivery, or stillbirth is uncertain.

Increasing evidence indicates that chlamydial infection in pregnancy is a risk marker for premature
delivery and postpartum infections. Women at greatest risk are those with recent chlamydial infection
detected by anti-chlamydial IgM. Those with chronic or recurrent infection do not have increased risk
for preterm delivery. It is hypothesized that asymptomatic cervicitis predisposes to mild amnionitis.
This event activates phospholipase A2 to release prostaglandins, which cause uterine contractions that
may lead to premature labor. Chlamydial infection is associated with higher rates of early postpartum
endometritis as well as delayed infection from Chlamydia that often presents several weeks
postpartum.

Treatment

In most cases, Chlamydia can be eradicated from the cervix by doxycycline 100 mg orally twice daily for
7 days (for non-pregnant patients), or azithromycin 1 g orally as a single dose. Compliance with
treatment may play a major role in controlling chlamydial infections. One group of researchers
evaluated the compliance with anti-chlamydial and antigonorrheal therapy and found that 63% of
patients treated with the standard 7-day regimen of tetracycline or erythromycin were compliant. An
alternate regimen is erythromycin base 500 mg or erythromycin ethylsuccinate 800 mg orally 4 times
daily given for a minimum of 7 days. Patients who cannot tolerate erythromycin should consider
ofloxacin 300 mg twice daily or levofloxacin 500 mg orally once daily for 7 days. Administration of high
doses of ampicillin has resulted in elimination of C. trachomatis from the cervices of women with acute
salpingitis. Addition of the irreversible β-lactamase enzyme inhibitor sulbactam increases in vitro anti-
chlamydial activity.

Pregnant women are advised to take erythromycin base 500 mg 4 times daily for 7 days, or amoxicillin
500 mg 3 times daily for 7 days. Alternate regimens include erythromycin base 250 mg orally 4 times
daily for 14 days, erythromycin ethylsuccinate 800 mg orally 4 times daily for 7 days, erythromycin
ethylsuccinate 400 mg orally 4 times daily for 14 days, or azithromycin 1 g orally as a single dose. In
addition, we can prescribe anti-oxidants, vitamins, physical therapy, and eubiotics to adjust the vaginal
microflora. 

Current studies indicate that 3–5% of pregnant women and as many as 15% of sexually active non-
pregnant women have an asymptomatic chlamydial cervical colonization. Whether attempts
to eradicate asymptomatic colonization will prevent chlamydial cervicitis, salpingitis, or neonatal
infections is not known. Post-treatment cultures are not usually advised if doxycycline, azithromycin, or
ofloxacin is taken as described above and symptoms are not present; cure rates should be higher than
95%. Retesting may be considered 3 weeks after completing treatment with erythromycin. A positive
post-treatment culture is more likely to represent noncompliance by the patient or sexual partner or
reinfection rather than antibiotic resistance. It is important to ensure that the sexual partner is treated,
as most post-treatment reinfections occur because the sexual partner was not treated. Clinicians
should advise all women with chlamydial infection to be re-screened 3–4 months after treatment
before sexual intercourse is resumed.

Vaccine

Currently, vaccines against urogenital chlamydia are not presence, but studies in this area has been
conducted for over 10 years by ANTEX INC biologics, which has already created vaccines prototypes
TRACVAX (Chlamydia trachomatis vaccine) and TWARVAX (Chlamydia pneumoniae vaccine). They are
currently undergoing preclinical test. Experiments show that the vaccine protected the animals from
TRACVAX infertility caused by Chlamydia trachomatis infection.