Chlamydia and LGV: Screening and diagnostic testing

Screening and diagnostic testing guidance for Chlamydia trachomatis infections (including lymphogranuloma venereum (LGV)).

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Screening

C. trachomatis

Screening for C. trachomatis is recommended for anyone with risk factors for infection. Screening is effective for detecting and treating asymptomatic infections as well as preventing complications, transmission and reinfection.

Although females experience the majority of chlamydia infectionsFootnote 1, asymptomatic males under 25 can be a reservoir for infection and reinfection of their sexual partners.Footnote 2 Additional data are needed to determine whether routine screening of asymptomatic young males decreases the incidence of anogenital chlamydia infection in women.Footnote 3Footnote 4

The use of non-invasive samples (urine or self-obtained vaginal swab) can increase acceptance of screening for C. trachomatis infection. Depending on type of sexual activity, it may be necessary to collect specimens from multiple anatomical sites.

Screening recommendations for the detection of C. trachomatisFootnote 5Footnote 6:

Annual screening Targeted screening
  • Offer screening and repeat screening based on risk factors in those ≥ 25 years old
  • Screen at first prenatal visit. Rescreening at third trimester is indicated for those who test positive or who are at ongoing risk of infectionFootnote 17Footnote 18Footnote 19
  • Neonates born to women with chlamydia

LGV 

Routine LGV genotyping of asymptomatic chlamydia infections is not recommended. Consider LGV genotyping when an asymptomatic rectal chlamydia infection is diagnosed in gay, bisexual and other men who have sex with men (gbMSM) with risk factors for LGV.

Other Sexually transmitted and blood-borne infections (STBBIs)

STBBI screening varies by age, gender/sex, medical and sexual history. Screen anyone who presents with STBBI risk factors and treat as appropriate to prevent transmission and reinfection.

People with Neisseria gonorrhoeae often have a co-infection with C. trachomatis.Footnote 20Footnote 21

Infection with C. trachomatis can increase the risk of acquisition and transmission of human immunodeficiency virus (HIV).Footnote 22Footnote 23Footnote 24

People being evaluated or treated for a chlamydia infection should be screened for:

Because of high rates of co-infection, people being evaluated or treated for LGV should be screened for:

Diagnostic testing

C. trachomatis

Clinical presentation and sexual history determine which specimens should be collected and the type of test to use.

Nucleic Acid Amplification Tests (NAATs) are the most sensitive test for C. trachomatis.Footnote 26Footnote 27 Culture for C. trachomatis is no longer routinely available in Canada. Results are highly dependent on the type of test, specimen collection / transport and laboratory expertise. Consult with local laboratory regarding available tests, specimen collection and test performance.

NAAT does not differentiate between LGV and non-LGV genotypes.

Use NAAT whenever possible for urine and urethral, cervical or vaginal swabs.

Check with local laboratory about the availability of NAAT for testing of extra-genital specimens. Validated NAAT for rectal specimens are available in most jurisdictions, if unavailable check if culture is still available.

Consult with provincial and territorial guidelines or local laboratory regarding the use of NAAT for medico-legal purposes.

Based on expert opinion, that NAAT can detect small amounts of DNA or RNA (inoculum), post-exposure testing using NAAT can be done without waiting for 48 hours.

People with suspected LGV: If there has been travel to regions where chancroid (Haemophilus ducreyi) and donovanosis/granuloma inguinale (Klebsiella granulomatis) are endemic, these conditions should also be considered as differential diagnoses.

Recommended specimens and tests for C. trachomatis

Asymptomatic

Test Specimens for asymptomatic males Specimens for asymptomatic females
NAAT First-void urine Vaginal swab, self-obtained or collected by a clinician
or
First-void urine
or
Cervical swab
Based on history: conjunctival, pharyngeal and/or rectal swabs

Note: Urine specimens should be first-void urine (initial 10 to 20 mL of the urine stream). Ideally, the person should not have voided for at least two hours prior to urine or urethral swab specimen collection. More recent voiding does not preclude testing.Footnote 5

Symptomatic

Physical examination is essential when an STI is suspected. Collect specimens based on clinical presentation and sexual history, prior to treatment.

Test Specimens for symptomatic malesFootnote 5 Specimens for symptomatic femalesFootnote 5

NAAT

  • First-void urine
  • Urethral swab
  • Rectal swab
  • Pharyngeal swab
  • First-void urine
  • Cervical swab
  • Vaginal swab
  • Rectal swab
  • Pharyngeal swab
  • Swab of the lesion
  • Fluid from buboes
  • Conjunctival swab

Due to high rates of concomitant infection, also collect specimens for the diagnosis of gonococcal infections by NAAT and culture.Footnote 21 NAAT can detect both C. trachomatis and Neisseria gonorrhoeae from a single specimen.

LGV

LGV diagnosis is not straightforward. It is often based on history and clinical presentation, supported by laboratory testing. Clinicians should have a high index of suspicion for LGV in people who present with consistent signs/symptoms (e.g. proctitis and/or marked inguinal or femoral lymphadenopathy or buboes) and/or if their history suggests exposure.

Identification of C. trachomatis in bubo fluid is highly suggestive of LGV, even prior to or without identification of LGV genotypes. Buboes caused by LGV usually contain a small amount of milky fluid. Aspirate buboes through healthy skin; an injection of 2 to 5 mL sterile saline may be required.

Genotyping

Genotyping of positive specimens for C. trachomatis is necessary for a definitive diagnosis of LGV.

C. trachomatis-positive specimens from people with symptoms compatible with LGV and from sexual partners of people diagnosed with LGV should be forwarded to a provincial/territorial laboratory or the National Microbiology Laboratory (NML) for LGV genotyping.

Published data on LGV in gbMSM have found that few urine samples or urethral swabs test positive for LGV when C. trachomatis is identified.Footnote 28Footnote 29Footnote 30Footnote 31Footnote 32

For gbMSM with risk factors for LGV, consider LGV genotyping of rectal specimens with positive C. trachomatis results. Although earlier studies identified rectal LGV primarily in symptomatic peopleFootnote 28Footnote 29Footnote 33, a 2017 study from the Netherlands found that a high proportion of chlamydia-positive rectal specimens tested positive for LGV in asymptomatic gbMSM.Footnote 30

Anoscopy/sigmoidoscopy/proctoscopy

Anoscopy/sigmoidoscopy/proctoscopy may reveal a pattern that resembles ulcerative colitis and/or granular or ulcerative proctitis in people with LGV.Footnote 34

Serology

Serology is not recommended for LGV diagnosis, due to cross-reactions with other C. trachomatis species and difficulties interpreting variations in titres. Because of the invasive nature of LGV, serology titres are generally significantly higher in LGV than in non-LGV chlamydia infections. Although high-titre serology is suggestive of LGV infection, it does not allow for a definitive diagnosis. Conversely, low-titre serology does not eliminate the possibility of current or past LGV infection. Because the duration of antibody response has not been defined, serology should not be used to assess treatment response.

References

Footnote 1

Choudhri Y, Miller J, Sandhu J, Leon A, Aho J. Chlamydia in Canada, 2010-2015. Can Commun Dis Rep 2018 Feb 1;44(2):49-54.

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Footnote 2

Dielissen PW, Teunissen DA, Lagro-Janssen AL. Chlamydia prevalence in the general population: is there a sex difference? a systematic review. BMC infectious diseases 2013;13(1):534.

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Footnote 3

US Preventive Services TF. Chlamydia screening among sexually active young female enrollees of health plans--United States, 2000-2007. MMWR Morb Mortal Wkly Rep 2009;58(14):362-365.

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Footnote 4

Meyers D.S., Halvorson H., Luckhaupt S. Screening for chlamydial infection: An evidence update for the U.S. Preventive Services Task Force. Ann Intern Med 2007;147(2):135-142.

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Footnote 5

Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae--2014. MMWR Recomm Rep 2014 Mar 14;63(RR-02):1-19.

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Footnote 6

Public Health Agency of Canada. Section 2: Canadian Guidelines on Sexually Transmitted Infections – Primary care and sexually transmitted infections. 2013; Available at: https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/sexually-transmitted-infections/canadian-guidelines-sexually-transmitted-infections-17.html#a2. Accessed May,16, 2019.

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Footnote 7

Marrazzo JM, Whittington WL, Celum CL, Handsfield HH, Clark A, Cles L, et al. Urine-based screening for Chlamydia trachomatis in men attending sexually transmitted disease clinics. Sex Transm Dis 2001 Apr;28(4):219-225.

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Footnote 8

Andersen B, Olesen F, Moller JK, Ostergaard L. Population-based strategies for outreach screening of urogenital Chlamydia trachomatis infections: a randomized, controlled trial. J Infect Dis 2002 Jan 15;185(2):252-258.

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Footnote 9

Braverman PK, Biro FM, Brunner RL, Gilchrist MJ, Rauh JL. Screening asymptomatic adolescent males for chlamydia. J Adolesc Health Care 1990 Mar;11(2):141-144.

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Footnote 10

Chernesky MA, Jang D, Lee H, Burczak JD, Hu H, Sellors J, et al. Diagnosis of Chlamydia trachomatis infections in men and women by testing first-void urine by ligase chain reaction. J Clin Microbiol 1994 Nov;32(11):2682-2685.

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Footnote 11

Moncada J, Schachter J, Shafer MA, Williams E, Gourlay L, Lavin B, et al. Detection of Chlamydia trachomatis in first catch urine samples from symptomatic and asymptomatic males. Sex Transm Dis 1994 Jan-Feb;21(1):8-12.

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Footnote 12

National Chlamydia Screening Programme Steering Group. New Frontiers – National Chlamydia Screening Programme Annnual Report 2005/6. Health Protection Agency 2006.

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Footnote 13

Ciemins EL, Kent CK, Flood J, Klausner JD. Evaluation of chlamydia and gonorrhea screening criteria: San Francisco sexually transmitted disease clinic: 1997 to 1998. Sex Transm Dis 2000;27(3):165-167.

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Footnote 14

Marrazzo JM, White CL, Krekeler B, Celum CL, Lafferty WE, Stamm WE, et al. Community-based urine screening for Chlamydia trachomatis with a ligase chain reaction assay. Ann Intern Med 1997 Nov 1;127(9):796-803.

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Footnote 15

LaMontagne DS, Fine DN, Marrazzo JM. Chlamydia trachomatis infection in asymptomatic men. Am J Prev Med 2003 Jan;24(1):36-42.

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Footnote 16

Domeika M, Bassiri M, Mardh PA. Diagnosis of genital Chlamydia trachomatis infections in asymptomatic males by testing urine by PCR. J Clin Microbiol 1994 Oct;32(10):2350-2352.

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Footnote 17

Davies HD, Wang EE. Periodic health examination, 1996 update: 2. Screening for chlamydial infections. Canadian Task Force on the Periodic Health Examination. CMAJ 1996 Jun 1;154(11):1631-1644.

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Footnote 18

Centers for Disease Control and Prevention (CDC). Sexually Transmitted Diseases Treatment Guidelines, 2006. MMWR Recommendations and Reports August 4, 2006;55(11):1-94.

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Footnote 19

Ryan GM,Jr, Abdella TN, McNeeley SG, Baselski VS, Drummond DE. Chlamydia trachomatis infection in pregnancy and effect of treatment on outcome. Am J Obstet Gynecol 1990 Jan;162(1):34-39.

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Footnote 20

Creighton S, Tenant-Flowers M, Taylor C, Miller R, Low N. Co-infection with gonorrhoea and chlamydia: how much is there and what does it mean? Int J STD AIDS 2003;14(2):109-113.

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Footnote 21

Lyss SB, Kamb ML, Peterman TA, Moran JS, Newman DR, Bolan G, et al. Chlamydia trachomatis among patients infected with and treated for Neisseria gonorrhoeae in sexually transmitted disease clinics in the United States. Ann Intern Med 2003;139(3):178-185.

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Footnote 22

Fransen L, Avonts D, Piot P. Treatment of genital chlamydial infection with ofloxacin. Infection 1986;14(suppl 4):S318.

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Footnote 23

Batteiger B, Jones R, White A. Efficacy and safety of ofloxacin in the treatment of nongonococcal sexually transmitted disease. . Am.J.Med. 1989;87(6C):75S.

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Footnote 24

Nayagam A, Ridgway G, Oriel J. Efficacy of ofloxacin in the treatment of non-gonococcal urethritis in men and genital infections caused by Chlamydia trachomatis in men and women. J Antimicrob Chemother 1988;22(suppl C):155.

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Footnote 25

Boutin CA, Venne S, Fiset M, Fortin C, Murphy D, Severini A, et al. Lymphogranuloma venereum in Quebec: Re-emergence among men who have sex with men. Can Commun Dis Rep 2018 Feb 1;44(2):55-61.

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Footnote 26

Association of Public Health Laboratories. Laboratory Diagnostic Testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Expert Consultation Meeting Summary Report January 13-15, 2009.

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Footnote 27

Kapala J, Biers K, Cox M, Kamionka M, Sumner J, Toor R, et al. Aptima Combo 2 testing detected additional cases of Neisseria gonorrhoeae infection in men and women in community settings. J Clin Microbiol 2011 May;49(5):1970-1971.

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Footnote 28

Nieuwenhuis RF, Ossewaarde JM, Götz HM, Dees J, Thio HB, Thomeer MG, et al. Resurgence of lymphogranuloma venereum in Western Europe: an outbreak of Chlamydia trachomatis serovar l2 proctitis in The Netherlands among men who have sex with men. Clinical infectious diseases 2004;39(7):996-1003.

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Footnote 29

Ward H, Alexander S, Carder C, Dean G, French P, Ivens D, et al. The prevalence of lymphogranuloma venereum infection in men who have sex with men: results of a multicentre case finding study. Sex Transm Infect 2009 Jun;85(3):173-175.

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Footnote 30

de Vrieze NHN, Versteeg B, Bruisten SM, van Rooijen MS, van der Helm JJ, de Vries HJC. Low Prevalence of Urethral Lymphogranuloma Venereum Infections Among Men Who Have Sex With Men: A Prospective Observational Study, Sexually Transmitted Infection Clinic in Amsterdam, the Netherlands. Sex Transm Dis 2017 Sep;44(9):547-550.

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Footnote 31

Desclaux A, Touati A, Neau D, Laurier-Nadalie C, Bebear C, de Barbeyrac B, et al. Extra-rectal lymphogranuloma venereum in France: a clinical and molecular study. Sex Transm Infect 2018 Feb;94(1):3-8.

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Footnote 32

Annan NT, Sullivan AK, Nori A, Naydenova P, Alexander S, McKenna A, et al. Rectal chlamydia--a reservoir of undiagnosed infection in men who have sex with men. Sex Transm Infect 2009 Jun;85(3):176-179.

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Footnote 33

Saxon C, Hughes G, Ison C, UK LGV Case-Finding Group. Asymptomatic Lymphogranuloma Venereum in Men who Have Sex with Men, United Kingdom. Emerg Infect Dis 2016 Jan;22(1):112-116.

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Footnote 34

Quinn TC, Goodell SE, Mkrtichian E, Schuffler MD, Wang S, Stamm WE, et al. Chlamydia trachomatis proctitis. N Engl J Med 1981;305(4):195-200.

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