CLAMIDIA

Chlamydiae are small gram-negative obligate intracellular microorganisms that preferentially infect squamocolumnar epithelial cells.
Chlamydia trachomatis is one of the 4 species (also includingChlamydia puerorum, Chlamydia psittaci, and Chlamydia pneumoniae) in the
genus Chlamydia. C trachomatis can be differentiated into 18 serovars (serologically variant strains) based on monoclonal antibodybased typing assays.
Serovars A, B, Ba, and C are associated with trachoma (a serious eye disease that can lead to blindness), serovars D-K are associated with genital tract
infections, and L1-L3 are associated with lymphogranuloma venereum (LGV).
Pathophysiology
The pathophysiologic mechanisms of chlamydiae are poorly understood at best. The initial response to infected epithelial cells is a neutrophilic infiltration
followed by lymphocytes, macrophages, plasma cells, and eosinophilic invasion. The release of cytokines and interferons by the infected epithelial cell
initializes this inflammatory cascade.
Infection with chlamydial organisms invokes a humoral cell response, resulting in secretory immunoglobulin A (IgA) and circulatory immunoglobulin M
(IgM) and immunoglobulin G (IgG) antibodies and a cellular immune response. Recent studies have implicated a 40-kd major outer membrane protein
(MOMP), as well as 10- and 60-kd chlamydial heat-shock proteins (cHSP), in the immunopathologic response, but further studies are needed to better
understand these cell-mediated immune responses.
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Chlamydiae have a unique biphasic life cycle that is adaptable to both intracellular and extracellular environments. In the extracellular milieu, the so-called
elementary body (EB) is found. EBs are metabolically inactive infectious particles; functionally, they are spore-type structures. Once inside a susceptible
host cell, the EB prevents phagosome-lysozyme fusion and then undergoes reorganization to form a reticulate body (RB).
The RB synthesizes its own DNA, RNA, and proteins but requires energy in the form of adenosine triphosphate (ATP) from the host cell. After a sufficient
amount of RBs have formed, some transform back into EBs, exiting the cell to infect others.
Frequency
I nternational
In recent reports, the World Health Organization (WHO) estimated 140 million cases of C trachomatis infection worldwide.
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Mortality/Morbidity
Although urogenital carriage of chlamydiae often is asymptomatic, the most common manifestation of disease is local mucosal inflammation associated
with a discharge, urethritis in the male, and urethritis/vaginitis/cervicitis in the female.
Chlamydia is one of the leading causes of pelvic inflammatory disease (PID) and infertility in women. The risk of ectopic pregnancy in women
who have had PID is 7-10 times greater than that for women without a history of PID. In 15% of women who have contracted PID, chronic abdominal pain
is a long-term manifestation that most likely is related to pelvic adhesions in the ovaries and fallopian tubes.
Chlamydial infections increase the risk for acquiring HIV infection by increasing genital mucosal inflammation.
Pregnant women infected with chlamydia can pass the infection on to their infants during delivery, which may develop into chlamydial
pneumonia or chlamydial conjunctivitis.
Race
The incidence of chlamydial infection is not related to race per se but rather to the sexual histories of the individuals and, particularly, to the frequency and
use (or nonuse) of barrier protection.
Sex
Although the presence of asymptomatic infection with genitourinary chlamydiae can differ, acquisition is similar for both sexes.
Age
Age factors in chlamydial genitourinary infection relate to the age of first sexual exposure and the frequency of exposure.
Clinical
History
C trachomatis is a sexually transmitted microorganism responsible for a wide spectrum of diseases that includecervicitis, salpingitis, endometritis,
urethritis, epididymitis, conjunctivitis, and neonatal pneumonia. In contrast to gonorrhea infection, most men and women who are infected are
asymptomatic, and, therefore, diagnosis is delayed until a positive screening result or upon discovering a symptomatic partner. In July 2007, The US
Preventive Services Task Force Screening released a new recommendation statement for chlamydial infections.
Routine chlamydia screening in sexually active young women is recommended to prevent consequences of untreated chlamydial infection (eg, pelvic
inflammatory disease, infertility, ectopic pregnancy, chronic pelvic pain). Fewer than half of young, sexually active females in the United States are
screened for chlamydia, reportsMorbidity and Mortality Weekly Report. Nationally, the annual screening rate increased from 25.3% in 2000 to 43.6% in
2006 and then decreased slightly to 41.6% in 2007.
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Chlamydia has been isolated in approximately 40-60% of males presenting with nongonococcal urethritis. Recent epidemiological studies indicate a high
prevalence rate of asymptomatic men who act as a reservoir for chlamydial infections. A study by Quinn et al (1996) demonstrated that transmission
probability in both men and women is estimated at 68%.
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Risk factors
o Nonwhite race
o Multiple sexual partners
o Age younger than 19 years
o Poor socioeconomic conditions
o Single marital status
o Nonbarrier contraceptive use
Neonatal risk
o Conjunctivitis
o Neonatal pneumonia
Physical
Women
o Easily induced endocervical bleeding
o Mucopurulent endocervical discharge
o Intermenstrual bleeding
o Cervical discharge
o Dysuria
o Abdominal pain
Men
o Urethral discharge
o Urinary frequency and/or urgency
o Dysuria
o Scrotal pain/tenderness
o Perineal fullness (related to prostatitis)
Differential Diagnoses
Herpes Simplex
Laboratory Studies
Because of the possibility of multiple sexually transmitted infections, all patients with any sexually transmitted disease (STD) should be
evaluated for chlamydial infection because chlamydial treatment is included in the Centers for Disease Control and Prevention (CDC) STD treatment
regimens.
Cytologic diagnosis
o This is used mainly for the diagnosis of infant inclusion conjunctivitis and in ocular trachoma by the demonstration of
intracytoplasmic C trachomatis inclusions in HeLa cells (ie, continuously cultured carcinoma cell line used for tissue cultures).
o Cytologic diagnosis also is used to evaluate endocervical scrapings, but interpretation is difficult and sensitivity and specificity have
been low.
Isolation in cell culture
o C trachomatis grows well in a variety of cell lines (eg, McCoy, HeLa cells) that can be maintained in tissue culture.
o Incubation in tissue culture is 40-72 hours, depending on the cell type and specific biovar.
o Intracytoplasmic inclusions can be detected either by Giemsa stains or by immunofluorescent staining with monoclonal antibodies.
o Because of its high specificity (100%) and sensitivity, cell culture is the only test that should be used to establish the presence or
absence of infections in cases with legal implications such as rape or sexual abuse.
Antigen detection and nucleic acid hybridization
o By direct fluorescent antibody (DFA)
o By enzyme-linked immunosorbent assay
o Detection of chlamydial ribosomal RNA (rRNA) by hybridization with a DNA probe
Advantage: This is simpler and less expensive. Most studies report sensitivities greater than 70% and specificities of 97-99%
in populations of men and women with a prevalence of infection of 5% or more. Antigen detection may well be the most appropriate diagnostic test for a
primary care setting in the United States if a definitive diagnostic test is required.
Disadvantage: It is less sensitive when compared to tissue culture. In low-prevalence populations (ie, <5% infected), a highly
significant proportion of positive test results are false-positive results. Therefore, verification of a positive test result is desirable in certain cases. Such
verification can be by culture (eg, a second nonculture test that identifies a different chlamydial antigen or nucleic acid sequence than the first test), a
blocking antibody, or competitive probe.
Detection of chlamydial genes by DNA amplification tests
o Polymerase chain reaction (PCR)
o Ligase chain reaction (LCR)
o Specific chlamydial rRNA using transcription-mediated amplification
o Both PCR and LCR detect C trachomatis in urine or self-administered vaginal swab specimens with sensitivity comparable to that with
urogenital swab specimens.
Serology
o Complement fixation test
All patients with LGV or psittacosis have complement-fixing antibody titers of greater than 1:16.
Fifteen percent of men with urethritis and 45% of women with endocervical infection have titers 1:16 or greater.
o Microimmunofluorescence test
This is more sensitive than complement fixation test.
Results are positive in 99% or more of women with cervicitis and in 80-90% of men with urethritis.
Antibody classes
o Antichlamydia IgM is uncommon in adults with genital tract infection.
o The prevalence of antichlamydia IgG is high in sexually active adults, even in those who do not have an active infection, and it likely is
due to past infection.
o A statistically significant association exists between chlamydia-specific serum IgA and active disease.
o The sensitivity, specificity, and predictive values are not high enough to make any serology clinically useful in the diagnosis of active
disease. Therefore, chlamydial serologies are not recommended for diagnosis of genital tract disease.
The choice of the most appropriate test depends on the clinical setting, the facilities available, and the relative cost.
Treatment
Medical Care
Patients should abstain from sexual intercourse for 7 days after single-dose therapy or until the end of a longer regimen.
Patients also should refrain from sexual intercourse until all of their sex partners have been cured.
Follow-up culture is not recommended after azithromycin or doxycycline therapy, but it may be considered in pregnancy after erythromycin or
amoxicillin therapy. Nonculture tests should be avoided in this circumstance to avoid positive results from nonviable organisms.
Medication
Treatment of genitourinary chlamydial infection clearly is indicated when the infection is diagnosed or suspected. Treatment also is indicated for sex
partners of the index case if the time of the last sexual encounter was within 60 days of onset, and it should be considered for longer periods for the last
sexual partner. Treatment of chlamydia is indicated for patients being treated for gonorrhea, as well.
The Centers for Disease Control and Prevention (CDC) updated treatment guidelines for gonococcal infection and associated conditions, which were
published in the April 13, 2007, issue of the Morbidity and Mortality Weekly Report.
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Fluoroquinolone antibiotics are no longer recommended to treat
gonorrhea in the United States. The recommendation was based on analysis of new data from the CDC's Gonococcal Isolate Surveillance Project (GISP).
The data from GISP showed the proportion of gonorrhea cases in heterosexual men that were fluoroquinolone-resistant (QRNG) reached 6.7%, an 11-fold
increase from 0.6% in 2001.
This limits treatment of gonorrhea to drugs in the cephalosporin class (eg, ceftriaxone 125 mg IM once as a single dose or a single PO dose of cefixime 400
mg).
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Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented..
Antibiotics
Therapy should cover all likely pathogens in the context of this clinical setting.
Azithromycin (Zithromax)
Relatively new member of the macrolide family of antimicrobials. Related to erythromycin, it is considered by many to be the treatment of choice of C
trachomatis genitourinary infection because it may be administered as a 1-dose treatment, which improves adherence to treatment.Adult:1 g PO once
Doxycycline (Doryx, Vibramycin)
Well absorbed tetracycline antimicrobial. When administered for 1 wk, appears to be as effective as single-dose azithromycin for genitourinary chlamydial
infections. Although the course is longer (7 d versus 1 dose) than azithromycin, the cost is less and it has been used in clinical practice for a much longer
time.Adult:100 mg PO bid
Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab, Erythrocin)
Macrolide antimicrobial agent that generally is considered the recommended treatment for chlamydial genitourinary infection only during
pregnancy.Adult:500 mg erythromycin base PO qid for 7 d; alternatively, 250 mg erythromycin base PO qid for 14 d or 800 mg erythromycin
ethylsuccinate PO qid for 7 d or 400 mg qid for 14 d
Ampicillin (Principen, Omnipen, Marcillin)
Like erythromycin, amoxicillin is considered a recommended treatment for genitourinary chlamydial infection only in pregnant women.Adult:500 mg PO
tid for 7 d