OVERVIEW: What every clinician needs to know

Pathogen name and classification

Chlamydia trachomatis(C. trachomatis)is a Gram-negative coccoid or rod-shaped bacteria that causes genitourinary tract and eye infections.

What is the best treatment?

Table I describes treatment for conditions caused by C. trachomatis. Drug resistance to azithromycin or doxycycline has not been described to date.

How do patients contract chlamydia trachomatis, and how do I prevent spread to other patients?

  • C. trachomatis is comprised of serovars that cause distinct clinical syndromes. Serovars A, B, Ba, C cause trachoma. Servars D-K cause genital infections, and serovars L1, L2, L3 cause lymphogranuloma venereum (LGV).

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  • C. trachomatis can be spread via sexual contact, or via contact with infected secretions.

  • The organism is found worldwide and has no non-human reservoir.

Genital chlamydia infections
  • C. trachomatis infection is the most common bacterial sexually transmitted infection worldwide, and the most common reportable disease in the United States, with 1.3 million cases in 2010.

  • True trends in prevalence are difficult to parse, as over the past decades, more states have instituted mandatory laboratory and provider reporting to local and state health departments. Test technology has also become more sensitive with the switch from cell culture to nucleic acid amplification testing (NAAT). In addition, chlamydia screening in women has been added as a quality measure for insurance plans and managed care organizations. All of these factors have contributed to an increase in reported cases.

  • While chlamydia screening is recommended by U.S. guidelines for all sexually active women younger than age 26, there is no similar recommendation for men who have sex with women. Therefore, the known cases of genital chlamydia infections in men depend largely on reporting of symptomatic cases, or partners of women with a diagnosed infection.

  • For men who have sex with men (MSM) who practice receptive anal sex, rectal chlamydia infections are common, and most are asymptomatic.

  • LGV is endemic in South and Southeast Asia, the Caribbean, and Africa.

  • It had been most commonly described as a rare sexually transmitted infection in heterosexuals, until the early 2000s when outbreaks occurred in MSM in the Netherlands, England and New York City.

  • The MSM cases were associated with being HIV-infected, and with engaging in traumatic sexual practices. Unlike heterosexual cases, they most commonly presented with bloody proctitis.

  • C. trachomatis serovars A, B, Ba, C that cause trachoma are endemic worldwide, but clinical disease affects primarily poor and rural populations in countries within Africa, Asia, the Middle East, South and Central America, Pacific Islands and in parts of Australia.

  • The World Health Organization (WHO) estimates that trachoma is responsible for 3% of the word’s blindness, with 21 million people currently infected.

  • In hyperendemic areas, prevalence is highest in pre-school age children, with up to 60-90% infected.

  • Transmission occurs by direct contact with secretions from the eyes, throat and nose of infected persons.

  • Recurrent infection leading to chronic inflammation and scarring are required for visual impairment, which most often occurs in middle aged persons.

  • Women, perhaps due to close proximity to infected children, are at higher risk for eventual vision impairment and blindness than men.

  • Flies can act as a vector of infection by physically transmitting secretions from an infected person to an uninfected person.

  • There is no non-human reservoir. The risk of infection increases with poverty, crowding, presence of flies, and poor hygiene.

Infection control issues
  • All serovars of C. trachomatis are transmitted by intimate contact with an infected person, either sexual (genital chlamydia, LGV) or through oral, ocular or nasal secretions.

  • Condoms used correctly and consistently are protective against sexual transmission of genital C. trachomatis.

  • There are fewer data about the effectiveness of condoms for preventing LGV infection, but many public health agencies recommend their use to decrease risk of transmission.

  • For both genital chlamydia and LGV, treatment of sexual partners is recommended to reduce risk of reinfection in the original patient.

  • Trachoma can be prevented by reducing crowding, improving hygiene, and control of flies.

  • In hyperendemic areas, annual mass treatment of communities with single dose azithromycin has been utilized by WHO as a trachoma control strategy.

  • There are currently no vaccines available against C. trachomatis.

What host factors protect against chlamydia trachomatis?

  • Natural infection with C. trachomatis does not confer long-lasting protection against reinfection.

  • However, partial immunity has been hypothesized based on studies in STD clinic patient populations.

  • Animal models of genital infection implicate Th1 CD4 cells as important to resolving infection, as well as antibodies directed against membrane proteins. So both cell mediated and antibody responses are likely important.

  • Patients with prior sexually transmitted infections, and with multiple or concurrent sex partners are at increased risk for genital chlamydia and LGV.

  • In the cases of LGV proctitis in men who have sex with men, HIV-infection was associated with an increased risk of infection.

  • LGV proctitis outbreaks in MSM have also been associated with unprotected anal sex and insertion of one partner’s hand into the rectum of another partner (fisting).

  • Individuals, especially children and their caretakers, who live in poor, rural areas in developing countries are at increased risk for trachoma.

  • After initial infection with C. trachomatis, there is a neutrophilic infiltration followed by lymphocytes, macrophages and plasma cells.

  • With the trachoma serovars, lymphoid follicles form. Epithelial proliferation can occur, and as the initial inflammation resolves, scarring can result.

  • Reinfection after resolution of an initial genital or eye infection with C. trachomatis results in an exuberant inflammatory response, and genital infection has been shown in some studies to be long-lasting in women without treatment, leading to chronic inflammation.

What are the clinical manifestations of infection with chlamydia trachomatis?

Genital chlamydia infections
  • Uncomplicated genital infection is largely asymptomatic in women, but may cause dysuria, genital irritation, vaginal discharge or dyspareunia.

  • Women with pelvic inflammatory disease (PID) may have lower abdominal pain, fever and tenderness of the cervix, uterus, or adnexae on pelvic examination.

  • Fitz-Hugh Curtis syndrome presents with pain in the right upper quadrant in women with PID and is caused by perihepatitis due to the genital tract infection.

  • Men may also be asymptomatic, particularly in rectal infections of MSM. Symptoms vary by site of infection and may include urethral irritation or discharge, dysuria, rectal pain or discharge, and tenesmus.

  • Chlamydia epididymitis presents with unilateral supratesticular pain and swelling.

  • Chlamydia prostatitis presents much like any other chronic prostatitis, and patients may have pelvic pain, urinary frequency, dysuria, and low fever.

  • Reactive arthritis following genital chlamydia infection (formerly known as Reiter’s syndrome) can include asymmetric arthritis, conjunctivitis and balanitis.

  • Chlamydia conjunctivitis can be caused by serovars D-K (this is distinct from trachoma) and presents with erythema and sometimes a cobblestone appearance.

  • LGV in heterosexual populations presents initially with a transient papule on the genitals which is often not noticed before it ulcerates and then resolves. This is then followed by enlargement of the inguinal lymph nodes, which can become very inflamed, tender and may drain pus – this finding is known as a bubo.

  • LGV proctitis in MSM may present with severe friability and bleeding of the rectal mucosa, along with discharge, pain, and tenesmus.

  • Trachoma initially may present in children with a follicular conjunctivitis. The follicles are pale, and are primarily found under the upper eyelid.

  • In adults who have had repeated infections over time, trachoma manifests with more chronic changes including eyelid scarring and inward contraction (entropion), which eventually causes eyelash inversion (trichiasis) and scarring of the globe.

What common complications are associated with infection with chlamydia trachomatis?

  • Genital chlamydia infection in women may lead to the complications of PID, perihepatitis, tubo-ovarian abscess, tubal pregnancy, and infertility.

  • Infection in pregnant women puts the neonate at risk for conjunctivitis and pneumonitis.

  • Infection in men may result in epididymitis and prostatitis.

  • Persons with chlamydia infection are at risk for reactive arthritis, which may include not only arthritis, but conjunctivitis and balanitis.

  • Genital chlamydia, including both uncomplicated rectal chlamydia and LGV in MSM, has been associated with an increased risk of acquiring HIV infection.

  • Untreated, trachoma can lead to blindness.

How should I identify the chlamydia trachomatis?

  • The diagnostic test of choice for genital chlamydia infections are nucleic acid amplification tests (NAAT). Optimal specimens include first catch urine for men, and vaginal swabs for women (although urine may also be used for women).

  • NAAT are also recommended for rectal infection in MSM, but are not FDA-approved for this site of infection. Individual laboratories may perform validation procedures in order to test these specimens and report results for clinical use.

  • Rapid antigen or antibody based tests for C. trachomatis are not yet commercially available in the U.S., but several are in development.

  • Culture is the gold standard for diagnosing C. trachomatis infections, but requires specialized laboratory capacity for cell culture and is not readily available outside of research settings.

  • Serology is not recommended for the routine diagnosis of C. trachomatis, but may be helpful in limited cases – infectious disease consultation should be obtained.

  • The diagnosis of trachoma is largely clinical in hyperendemic areas, but NAAT and other tests may be useful to confirm cases as prevalence decreases.

How does chlamydia trachomatis cause disease?

  • Full details of the pathogenic mechanisms of C. trachomatis are not well understood.

  • The LGV serovars enter through skin breaks or through the genital mucosa, travels to regional lymph nodes, and forms the characteristic granulomas called buboes seen in classic genital LGV.

  • LGV proctitis can cause intense inflammation of the rectal mucosa resulting in friable tissue and frank bleeding.

  • C. trachomatis can down regulate host immune responses; for example by secreting proteins intracellularly that degrade transcription factors needed for HLA I and II.

  • C.trachomatis can induce cytokine production, including IFN gamma by release of lipopolysaccharide.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Rekart, ML, Gilbert, M, Meza, R, Kim, PH, Chang, M, Money, DM, Brunham, RC. “Chlamydia Public Health Programs and the Epidemiology of Pelvic Inflammatory Disease and Ectopic Pregnancy”. J Infect Dis. 2012 Nov 16. (Population based study to address whether public health screening programs intended to control chlamydia are associated with increased genital chlamydia diagnoses, decreasing PID and other complications.)

Baneke, A. “Review: Targeting trachoma: Strategies to reduce the leading infectious cause of blindness”. Travel Med Infect Dis.. vol. 10. 2012 Mar. pp. 92-6. (Overview of the public health response to trachoma.)

Workowski, KA, Berman, SM. “Centers for Disease Control and Prevention Sexually Transmitted Disease Treatment Guidelines”. Clin Infect Dis.. vol. 53. 2011 Dec. pp. S59-63. (U.S. Guidelines for STD treatment, including genital chlamydia and its complications and LGV.)

Howie, SE, Horner, PJ, Horne, AW, Entrican, G. “Immunity and vaccines against sexually transmitted chlamydia trachomatis infection”. Curr Opin Infect Dis.. vol. 24. 2011 Feb. pp. 56-61. (Overview of the immune system response to C. trachomatis and work to date on vaccine development.)

Paavonen, J. “Chlamydia trachomatis infections of the female genital tract: state of the art”. Ann Med.. vol. 44. 2012 Feb. pp. 18-28. (Broad overview of C. trachomatis genital tract infections in women.)

Richardson, D, Goldmeier, D. “Lymphogranuloma venereum: an emerging cause of proctitis in men who have sex with men”. Int J STD AIDS. vol. 18. 2007 Jan. pp. 11-4. (Describes the emergence in early Europe and elsewhere of LGV.)