Genital Chlamydia infection

 

Introduction

 

Genital Chlamydia infection is one of the most commonly reported STIs globally. Vertical transmission during childbirth can also occur. It causes inflammation of the genital and rectal mucous membranes as well as the conjunctiva, but is often asymptomatic. The causative organism, Chlamydia trachomatis, is an exclusively human, obligate, intracellular bacterial pathogen with a complex life cycle.

 

Chlamydia trachomatis serovars A–C are responsible for ocular trachoma, which is a major cause of blindness worldwide. Genital Chlamydia D–K strain infections are considered the world's most common sexually transmitted bacterial pathogens. Chlamydia trachomatis serovars L1–L3 cause lymphogranuloma venereum (LGV).

Chlamydia causes a number of clinical syndromes including urethritis, cervicitis, epididymo‐orchitis, pelvic inflammatory syndrome, seronegative reactive arthritis and ophthalmia neonatorum.

 

Epidemiology

 

Incidence and prevalence

 

In 2008, the WHO reported a global incidence of genital chlamydia and gonorrhoea with >100 million cases of each. However, genital chlamydia is considered to be at least three times more prevalent than gonorrhoea.

 

Age

 

Age is the most significant risk factor for chlamydia, with the highest rates being found in those under 25 years old and a decreasing prevalence with increasing age.

Sex

 

Chlamydial infection in women is 2.5 times more than men.

 

Associated diseases

 

Individuals diagnosed with an STI are at risk of other coexistent STIs, therefore a sexual health assessment is warranted.

 

Predisposing factors

 

The main predisposing factor for Chlamydia infection appears to be an age of less than 25 years. Cervical ectopy, where there is visible columnar epithelium on the ectocervix, is more common in younger women and the prevalence of chlamydia is greater in women with ectopy than without.

 

Pathology

 

Sub-acute and chronic asymptomatic infection is common and the infection can persist for many months or years if untreated. The frequent absence of symptoms in the acute phase facilitates spread.

The clinical manifestations of Chlamydia infection are probably a direct result of tissue damage as well as host immune response, resulting in scarring of the affected mucous membranes.

  

Causative organisms

 

Chlamydiae are obligate intracellular parasites and exhibit a unique, two‐stage developmental cycle with two forms:

·        An extracellular, infectious elementary body (EB).

·        An intracellular, replicative reticulate body (RB).

This cycle begins when infectious, metabolically inert EBs attaches to and stimulate uptake by the host cell. The internalized EB remains within a host‐derived vacuole, termed an inclusion, and differentiate into a larger, metabolically active RB. The RB multiplies by binary fission, and after 8–12 rounds of multiplication, the RBs differentiate to EBs asynchronously. At 48–72 h post‐infection, EB progeny are released from the host cell to initiate another cycle.

C. trachomatis strains A–K primarily infect squamocolumnar epithelial cells.

 

 

                          The life cycle of Chlamydia trachomatis

 

Clinical features

 

Asymptomatic infection occurs in up to 90% of women and more than 50% of men.

 

In men, the most common manifestation of disease is anterior urethritis, characterized by a mucopurulent urethral discharge and dysuria, with an onset 1–3 weeks after intercourse with an infected partner. Note that the discharge due to Chlamydia is classically less purulent, less profuse, and less spontaneous when compared to urethral gonorrhea. Rectal infection may result in proctitis in men practising receptive anal intercourse which may be asymptomatic, but some will have symptoms resembling those seen with gonococcal proctitis. It is important to exclude LGV if rectal symptoms are present.

In women, the columnar epithelium of the endocervix is commonly affected. Common symptoms include inter menstrual or post coital bleeding and vague but persistent lower abdominal pain, vaginal discharge and dysuria. Typically, in such patients there are signs of mucopurulent cervicitis and/or contact bleeding.

Extragenital infections also occur. Pharyngeal infections are usually asymptomatic. Infection of the eye causes acute follicular conjunctivitis which is usually, but not always, associated with genital infection. Acute follicular conjunctivitis is usually associated with Chlamydia whereas chronic conjunctivitis may be seen in trachoma or lymphogranuloma venereum. Neonates may develop conjunctivitis and pneumonia after being infected from passage through the birth canal of an infected mother. Chlamydia in pregnancy may be associated with premature labor and preterm birth.

 

Complications and co‐morbidities

 

Complications mostly occur from ascending infections and possibly from dissemination, and are also associated with pregnancy and the neonatal period.

Ascending infection in men causes epididymo‐orchitis. Epididymo‐orchitis in those less than 35 years old is most likely to be caused by a sexually transmitted organism such as C. trachomatis. Thus, aside from urethral discharge, men may also present with unilateral scrotal pain and swelling. In those over 35 years old urological pathogens such as Escherichia coli, Klebsiella sp. or enterococci are more likely.

Chlamydia should be considered as a possible cause for a Bartholin abscess, with or without concurrent gonococcal infection. In the absence of treatment, 10–40% of women infected with Chlamydia will develop PID, with ascending infection to the uterus and fallopian tubes. Symptoms may include fever, lower abdominal pain, back pain, vomiting, vaginal bleeding, dyspareunia, and adnexal or cervical motion tenderness on physical examination. Sequelae of untreated infection include tubo-ovarian abscesses, ectopic pregnancies, chronic pelvic pain, and infertility due to chronic inflammation with resultant scarring. The risk of developing PID increases with each recurrence of C. trachomatis infection, as does the risk of reproductive sequelae. Five to ten percent of women with chlamydial PID may develop perihepatitis. Fitz‐Hugh–Curtis syndrome presents as upper‐right‐sided abdominal pain and fibrinous ‘violin‐string’ adhesions of the liver capsule as a consequence of perihepatitis.

Chlamydia is strongly associated with reactive arthritis and is termed sexually acquired reactive arthritis (SARA). Reactive arthritis can occur up to 1 month after symptoms of nongonococcal urethritis (NGU) due to chlamydia. Reactive arthritis can be defined as a sterile inflammatory arthritis following bacterial infection elsewhere. Individuals with the haplotype HLA-B27 are at increased risk of developing the reactive arthritis syndrome. SARA occurs in 0.8–4% of those infected with Chlamydia. It is a seronegative, asymmetrical, spondyloarthropathy with or without extra‐articular features that include the following:

·        Mucocutaneous manifestations including circinate balanitis, erosions affecting the buccal and rectal mucosa and keratoderma blenorrhagica.

·        Iritis and conjunctivitis.

 

Prognosis and Clinical Course

Early treatment with appropriate antibiotic therapy results in excellent prognosis and reduces the risk of long-term complications, such as infertility from PID. It is important to complete an appropriate course of antibiotic.

  

Laboratory Tests

Traditionally, chlamydial infection was diagnosed by tissue culture with specimens obtained from the endocervix in women, urethra in men, and rectum, or conjunctivae, as indicated. More rapid and sensitive tests have replaced culture in recent years. A direct fluorescent antibody test, which is highly specific, can be performed on endocervical and penile urethral specimens with rapid results. Less invasive tests involving nucleic acid hybridization and nucleic acid amplification, such as PCR, is more commonly being used to detect even small amounts of chlamydial DNA in urethral, vaginal, endocervical swabs and in first voided urine samples. It should be noted that the nucleic acid amplification and hybridization tests are less accurate for chlamydial detection from rectal and oropharyngeal sites than from genital sites.

First‐void urine is the sample of choice in men, and in females a self‐taken vaginal swab or an endocervical swab are acceptable. In MSM and commercial sex workers, pharyngeal and rectal testing may also be indicated and NAATs are the only recommended test. Conjunctival sampling may also be clinically indicated in some situations.

There is also some debate about exactly who should receive chalmydial testing, aside from those whose symptoms suggest that diagnosis. The CDC recommends annual screening of all sexually active women under the age of 25 and for older women with risk factors (e.g., those who have a new sex partner or multiple sex partners).

 

Treatment

 

Treatment is indicated if chlamydia is diagnosed or if there is a history of contact with a person known to be infected. Patients with chlamydia should always be fully assessed and screened for other STIs and HIV. They should be asked to abstain from sexual contact for 7 days after they and their partners have received treatment and their symptoms have resolved.

Resistance in C. trachomatis has been infrequently reported and single‐dose azithromycin is the treatment of choice. It is not licensed in pregnancy but is recommended by the WHO.

In complicated infections, more prolonged courses of treatment are employed and specialist advice may be required.

 

Therapeutic ladder

Uncomplicated infection

First line

·        Azithromycin 1 g stat (including in pregnancy)

Second line

·        Doxycycline 100 mg b.d. for 7 days

Third line

·        Ofloxacin 200.300 mg b.d. for 7 days

·        Amoxicillin 500 mg four times a day for 7 days (pregnancy only)

 

Complicated infection

Chlamydial PID

·        Ceftriaxone 500 mg IM single dose+ oral doxycycline 100 mg twice daily and metronidazole 400 mg twice daily for 14 days

Or

·        Ofloxacin 400 mg PO twice daily + metronidazole 400 mg PO twice daily for 14 days (if gonorrhoea is unlikely)

Epididymo‐orchitis

·        Ceftriaxone 500 mg IM single dose+ doxycycline 100 mg PO twice daily for 10.14 days

Or

·        Ofloxacin 200 mg PO twice daily for 14 days (if gonorrhoea is unlikely)

Chlamydia‐associated reactive arthritis

·        Rest

·        Non‐steroidal anti‐inflammatory drugs

·        Seek specialist advice