Chlamydia

Article Author:
Michael Mohseni
Article Editor:
Veronica Takov
Updated:
2/4/2019 9:45:56 AM
PubMed Link:
Chlamydia

Introduction

Chlamydia is a sexually transmitted infectious disease caused by the bacterium Chlamydia trachomatis. In the United States, it is the most commonly reported bacterial infection. Globally, it is the most common sexually transmitted diseases. It causes an ocular infection called "trachoma," which is the leading infectious cause of blindness worldwide. In females, infertility and ectopic risks increase with Chlamydia trachomatis infections, leading to high medical costs.[1] Lymphogranuloma venereum (LGV), caused by distinct serovars of Chlamydia trachomatis, is a less common disease characterized by enlarged lymph nodes or severe proctocolitis.[2]

Etiology

Chlamydia trachomatis is part of the chlamydophila genus. These bacteria are gram-negative, anaerobic, intracellular obligates that replicate within eukaryotic cells. C. trachomatis differentiates into 18 serovars (serologically variant strains) based on monoclonal antibody-based typing assays. These serovars correlate with multiple medical conditions as follows[3]:

  • Serovars A, B, Ba, and C: Trachoma is a serious eye disease endemic in Africa and Asia that is characterized by chronic conjunctivitis and can lead to blindness

  • Serovars D-K: Genital tract infections

  • Serovars L1-L3: Lymphogranuloma venereum (LGV), which correlates with genital ulcer disease in tropical countries

Epidemiology

Urogenital chlamydia infections are the most commonly reported bacterial infections in the U.S and the most common cause of sexually transmitted disease in the world. The overall rate of urogenital infection amongst U.S. women is twice that among U.S. men, with a higher prevalence in women 15-24 years of age and a higher incidence in men between 20-24 years of age. 

Pathophysiology

Chlamydia is unique among bacteria, having an infectious cycle and two developmental forms.  These include the infectious form called the elementary body (EB) and the reticulate body (RB). The EB is metabolically inactive and is taken up by host cells. Within the host cell, the EB will differentiate into the metabolically active RB. The RB will then use host energy sources and amino acids to replicate and form new EB which can then infect additional cells. The target cells of C. trachomatis are the squamocolumnar epithelial cells of the endocervix and upper genital tract in women, and the conjunctiva, urethra, and rectum in both men and women. 

The bacterium is transmitted through direct contact with infected tissue, including vaginal, anal or oral sex, and can even be passed from an infected mother to the newborn during childbirth.

Histopathology

Typical intracytoplasmic inclusions and free chlamydiae are identifiable in Giemsa-stained cell scrapings from the eye. Stained conjunctival scrapings are positive in 90% of infants with neonatal conjunctivitis, and 50% of adults with inclusion conjunctivitis. Cytology techniques can be used to evaluate endocervical scrapings, but the sensitivity and specificity are low.[4]

History and Physical

C. trachomatis can lead to many urogenital infections including cervicitis, pelvic inflammatory disease, urethritis, epididymitis, prostatitis and lymphogranuloma venereum. Extragenital infections caused by C. trachomatis include conjunctivitis, perihepatitis, pharyngitis, reactive arthritis, and proctitis. 

Most commonly, patients remain asymptomatic reservoirs of the disease. In the minority of patients that are symptomatic, clinical signs depend on the location of the infection. Below are the common signs and symptoms associated with C. trachomatis urogenital infections.

  • Cervicitis: Approximately 70% of women will be asymptomatic or have mild symptoms such as vaginal discharge, bleeding, abdominal pain and dysuria.[5] Only a minority of women have the classic presentation of mucopurulent cervicitis with discharge and easily-induced endocervical bleeding.  
  • Pelvic Inflammatory Disease: This occurs when C. trachomatis ascends to the upper reproductive tract. Most commonly these patients will have abdominal or pelvic pain with or without signs and symptoms of cervicitis.
  • Urethritis: It is most commonly seen in men. There are subtle clinical differences between gonococcal urethritis and chlamydial urethritis, but making a reliable distinction without testing is not possible. It presents with dysuria and urethral discharge which is typically white, gray or sometimes clear, and may only be evident after penile "stripping" or during morning hours. 
  • Epididymitis: Typically, men will present with unilateral testicular pain and tenderness, possible hydrocele, palpable swelling of the epididymis and fever. 
  • Proctitis: Patients complain of rectal pain, discharge and bleeding in the setting of receptive anal intercourse. 
  • Lymphogranuloma venereum: Patients will present with a non-painful, small genital ulcer followed by the development of inguinal lymphadenopathy.

Evaluation

Among C. trachomatis infections, only trachoma is diagnosable on clinical grounds. Other chlamydial infections are associated with specific clinical syndromes but require laboratory confirmation. The gold standard for diagnosis of urogenital chlamydia infections is nucleic acid amplification testing (NAAT). This test is run on either the vaginal swabs for women or first-catch urine for men. Testing can also be performed on endocervical or urethral swabs. Alternative methods of testing include culture, rapid testing, serology, antigen detection and genetic probes. If there is no testing available, treatment is recommended based on clinical presentation.

Treatment / Management

The goal of treatment is the prevention of complications associated with infection (e.g., PID, perihepatitis), to decrease the risk of transmission, and the resolution of symptoms.  Treatment for uncomplicated urogenital chlamydia infection is with azithromycin. Doxycycline is an alternative, but azithromycin is preferred as it is a single-dose therapy.

Chlamydial infection and gonococcal infections often coexist. In men, the driver behind co-treatment for urogenital gonococcal infection should be by detection of the organism on NAAT or gram stain. In women, the gram stain is less helpful due to the possibility of normal Neisseria species colonization within the vaginal flora. Therefore, co-treatment should be dependent on an assessment of individual patient risk and local prevalence rates.

Patients should have partners identified and tested. They should also be counseled on high-risk behaviors, avoid sexual activity for one week after initiating therapy, and should consider testing for HIV.

Verification of cure should occur either three weeks after treatment completion, and retesting should be performed at three months after treatment.

If symptoms persist after treatment, consider coinfection with a secondary bacterium or reinfection. 

Differential Diagnosis

In the differential diagnoses, one should consider other infections that infiltrate the genital and urinary systems of men and women. Such diseases include: 

  • Bacterial vaginosis
  • Fitz-Hugh-Curtis syndrome
  • Mycoplasma genitalium infection
  • Periurethral abscess
  • Prostatitis
  • Salpingitis
  • Tubo-ovarian abscess
  • Ureaplasma infection

Treatment Planning

Uncomplicated Genital Chlamydia:

The World Health Organization (WHO) recommendations for treatment of uncomplicated genital chlamydia infections are the following:

  • Azithromycin 1 g by mouth as a single dose or
  • Doxycycline 100 mg by mouth twice daily for 7 days, or one of these alternatives: tetracycline 500 mg orally 4 times daily for 7 days, erythromycin 500 mg orally twice daily for 7 days, or ofloxacin 200-400 mg orally twice daily for 7 days

Anorectal Chlamydial infection:

In anorectal chlamydial infections, the WHO recommendation is oral doxycycline 100 mg twice daily for 7 days over oral azithromycin 1 g as a single dose.

Chlamydial infection in pregnancy:

WHO recommends the following for the treatment of chlamydial infection in pregnancy:

  • Azithromycin recommended over erythromycin, amoxicillin, and erythromycin
  • Azithromycin 1 g by mouth as a single dose or
  • Amoxicillin 500 mg orally 3 times daily for 7 days or
  • Erythromycin 500 mg orally twice daily for 7 days

Lymphogranuloma Venereum:

The WHO recommends the following for the treatment of lymphogranuloma venereum (LGV):

  • In adults and adolescents with LGV, the guidelines suggest doxycycline 100 mg orally twice a day for 21 days over azithromycin 1 g orally weekly for 3 weeks.
  • Good practice dictates the treatment of LGV, particularly for men who have sex with men and for people with HIV infection.
  • When contraindications to doxycycline are present, azithromycin should be the therapeutic choice.
  • When neither treatment is available, erythromycin 500 mg orally 4 times a day for 21 days is an alternative.
  • Doxycycline should not be used in pregnancy.

Prognosis

Antibiotic treatment has a 95% effectiveness rate for first-time therapy. The prognosis is excellent with prompt initiation of treatment early and with the completion of the entire course of antibiotics. Although treatment failures with primary therapies are quite rare, relapse may occur. Reinfection is common, and is usually related to nontreatment of infected sexual partners or acquisition from a new partner. Death is rare but can be caused by progression to salpingitis and tubo-ovarian abscess with rupture and peritonitis. The most significant morbidity occurs with repetitive infection with chlamydiae, which leads to scarring of the fallopian tubes and subsequent sterility.

Enhancing Healthcare Team Outcomes

In the United States and other developed countries, prevention of sexually transmitted genital infections and complications mainly focuses on screening and treating nonpregnant sexually active women aged 25 years or younger on an annual basis. Screening for pregnant women is recommended and screening and treatment of women over 25 years of age are recommendations if there are identifiable risk factors, such as new or multiple sexual partners. Screening of young men in high-risk settings (sexually transmitted disease and adolescent clinics, correctional facilities) should be a consideration if resources allow. Urine or endocervical NAAT are the recommended screening tests. The prognosis is excellent with prompt initiation of treatment early and with the completion of the entire course of antibiotics; antibiotic treatment is 95% effective for first-time therapy.

No vaccine is currently available for either trachoma or chlamydial genital infections.