Across the US and Canada, chlamydia and gonorrhea are the most commonly diagnosed bacterial sexually transmitted infections (STIs), and both are increasing in incidence.1-4 In Ontario, for example, chlamydia diagnoses increased from 21,872 (174.6/100,000) in 2005 to 41,833 (299.7/100,000) in 2016, and gonorrhea diagnoses rose from 3,325 (26.5/100,000) in 2005 to 6,780 (48.6/100,000) in 2016.5 Similar trends exist in other American and Canadian jurisdictions.2,6,7
Across both the US and Canada, these infections primarily affect patients younger than age 25, and although diagnoses are higher among females, a common risk factor is having heterosexual partners, suggesting that lower infection rates in males may be an effect of less screening among this group.2,3,7 Another factor contributing to a lack of screening is that these infections often present asymptomatically. Even when symptoms are not present, these STIs can cause negative sequelae for males and females, including pelvic inflammatory disease, epididymitis, and infertility.8,9
Clinicians need to know when and how to screen patients for these infections, especially considering new testing methods. This article reviews new Canadian guidelines and testing modalities for chlamydia and gonorrhea screening and provides an implementation approach. Although this discussion is primarily focused on public health standards and guidelines in Canada, these recommendations closely align with those of the US CDC.
Chlamydia. Although the clinical presentation of chlamydia can vary, it is often asymptomatic in males and females, and can cause infection of any mucosal membranes.8 Urethral symptoms of chlamydia may only be present in about 60% of males (and can be less common in females), and discharge, when present, may be scant and mucoid.10 Dysuria is often mild, described as an itching sensation in the distal urethra.8,9 Although these symptoms can be persistent, an intermittent presentation is also common, with patients describing either a presentation, resolution, and recurrence of symptoms, or prior symptoms that resolved spotaneously.8,9 Pharyngeal infections are virtually always asymptomatic, whereas rectal infections may be symptomatic and may include proctitis, rectal discharge, and tenesmus, when present.11 L-serovar Chlamydia trachomatis, known as lymphogranuloma venereum (LGV), may present with pronounced proctitis or proctocolitis-like symptoms, including abdominal and/or rectal pain, rectal discharge and/or bleeding, diarrhea, tenesmus, and possible fever or chills.12 A common differential diagnosis for LGV is inflammatory bowel disease.12
Gonorrhea. Although classically described as a symptomatic genital infection with profuse purulent urethral and/or vaginal discharge and persistent anterior urethral dysuria, gonorrhea can cause asymptomatic infections of the pharynx, urethra, cervix, and rectum.8,9 Approximately 90% of males with urethral gonorrhea experience these symptoms, but less than half of females with urethral and/or cervical infection are symptomatic.13 When present, symptoms among females can include increased vaginal discharge, dysuria, dyspareunia, and postcoital vaginal spotting.8,9
Compared with genital gonococcal infections, pharyngeal infections are often asymptomatic; analysis of 3,757 swabs at an STI clinic for men who have sex with men (MSM) identified no symptoms among the males identified as having these infections.11 With rectal infection, symptoms can be present and include anal discharge and discomfort, and possibly tenesmus.8,9
For anatomical location, Public Health Ontario shows that in Ottawa between June 1, 2016, and May 31, 2018, although the genital area is the most common site of chlamydia and gonorrhea infections, the pharynx or rectum was the only site of infection in about one-third of diagnoses among MSM. (See Infection site incidence, Ottawa, June 1, 2016, to May 31, 2018.) An important caveat for these data is that nucleic acid amplification testing (NAAT) for extragenital sites was not approved in Ontario until April 9, 2018; accordingly, these data compare NAAT for genital infections against culture for extragenital infections.14 This data table may therefore underrepresent the burden of extragenital STIs. Public Health Ontario speculates that extragenital sites are a reservoir for infection and that exclusive genitourinary testing contributes to ongoing transmission.14
Potential complications. Sequelae are possible in both chlamydia and gonorrhea. For women, this includes pelvic inflammatory disease, which develops when the infection spreads from the cervix to the upper reproductive tract and is characterized by pelvic or lower abdominal pain, dyspareunia, and postcoital bleeding; fever may also be present.8,15 On exam, there may be mucopurulent or purulent discharge from the cervical os, and cervical motion and/or adnexal tenderness.8 Acute pain is not necessary for diagnosis because pelvic inflammatory disease may be subclinical with only minimal pain and tenderness.15 As such, a high degree of clinical suspicion with a low threshold for diagnosis is recommended.8 For men, epididymitis is possible, which may present as insidious onset, mild, often unilateral testicular discomfort.8,16 On exam, erythema of the scrotum overlying the affected epididymis is possible, and on palpation there may be tenderness and edema of the affected site.8 Testicular edema and tenderness is possible in epididymo-orchitis.8 Patients with infectious epididymitis may have classic STI symptoms, including dysuria or discharge.8
Rarely, gonorrhea may produce a disseminated arthritis-dermatitis syndrome known as disseminated gonococcal infection, which usually manifests as asymmetric and migratory arthritis, affecting joints of the wrists, ankles, hands, and feet, with possible tenosynovitis.17 Approximately 2 to 10 painless pustular or vesiculopustular lesions may also arise on the distal extremities.17
Reactive arthritis is a similar complication, possibly occurring 1 to 4 weeks after chlamydia infection.18 With this, patients experience asymmetric oligoarthritis.18 While it was previously thought that reactive arthritis comprised a triad of arthritis, conjunctivitis, and urethritis, it is now understood that this triad is likely a clinical subset of reactive arthritis.19
Extragenital swab selection: NAAT vs. culture
Both the CDC and the Public Health Agency of Canada have updated their STI guidelines, recommending that NAAT be used for extragenital chlamydia and gonorrhea testing because it has superior sensitivity compared with culture.8,9 Based on published values from a validation study in Ontario (performed by Public Health Ontario using the Hologic Aptima Combo 2 Assay), extragenital culture compared with NAAT was overall 37% sensitive, identifying 200 of 535 infections, with detection rates ranging from 13% (n = 21/159) for pharyngeal gonorrhea to 67% (n = 103/153) for rectal gonorrhea.13,20,21 By comparison, the sensitivity for NAAT was 99.4% and 92.2% for pharyngeal and rectal chlamydia, and 100% for pharyngeal and rectal gonorrhea, respectively. The specificities were 99.9% for rectal and pharyngeal chlamydia, 98.25% for pharyngeal gonorrhea, and 99.0% for rectal gonorrhea.21
Based on these performance values, Public Health Ontario recommended extragenital NAATs only for patients deemed “high risk,” defined as patients who are contacts of someone diagnosed with one of these two STIs, MSM, and sex trade workers and their clients.14 The recommendation continued that patients not from these groups should have cultures done, although NAAT could be considered for low-risk patients based on clinical judgment and because of its higher sensitivity.14 Although Public Health Ontario did not specify its rationale, recommendations may have been based on the information that individuals without these characteristics were possibly underrepresented in the validation study sample, and the prevalence was so low for chlamydia and gonorrhea among the low-risk groups in the validation study that the positive predictive values made these tests less clinically useful.14
The most important aspect in assessing test performance in clinical practice is the prevalence of the condition that will be tested for among given patient populations. For example, the test for chlamydia has a sensitivity of 92.2% and specificity of 99.9% for pharyngeal infections. Even at a prevalence of 0.5%, among a sample of 1,000 patients, the test would likely detect all five of the infections (perhaps only four), and would generate only one false positive, yielding a positive predictive value exceeding 80%, which rivals the performance of the gonorrhea NAAT among high prevalence groups. For chlamydia, concerns about using NAAT for extragenital testing are less apparent based on test performance, which may reassure clinicians who prefer to opt for a test with sensitivity, provided that they proceed with the awareness that the positive predictive value for gonorrhea will likely be inferior. Such concerns, however, should be balanced against superior detection rates.
For pharyngeal gonorrhea, the test is 100% sensitive and 98.2% specific, meaning at a theoretical prevalence of 8% (as might be the case in a higher-risk population) among a sample of 1,000 patients, NAAT would accurately detect all 80 cases out of 1,000 individuals (yielding the prevalence of 8%) and would then generate an additional 18 false-positive results. The positive predictive value, which is calculated as the number of true positives divided by the total number of true and false positives, would be 81.6% (n = 80 / [80 + 18]).22 However, if gonorrhea prevalence were 0.5% (as may be the case in a lower risk population), the test would identify 5 positive cases and 18 false positives, yielding a positive predictive value of 21.7% (n = 5 / [5 + 18]). At 8% prevalence, four-fifths of the positive results identified by NAAT would be true positives, whereas at 0.5% prevalence, the opposite would be true; four-fifths of the cases identified by NAAT would be false negatives. The difference in these positive predictive values supports the focused NAAT use recommended by Public Health Ontario.
Two further items influence swab selection. The first relates to which swab should be used for patients with rectal symptoms. One approach would be to perform both NAAT and extragenital culture during initial testing. Whereas NAAT is highly sensitive and will likely detect any present STIs, only extragenital culture can generate information about antimicrobial resistance, which is important considering increasing resistance among gonococcal isolates across the US and Canada.23,24 This dual swab approach ensures that all specimen collection occurs during the first visit, and builds on the fact that gonorrhea, compared with chlamydia, is more likely to be symptomatic. To further minimize multiple visits, clinicians also empirically treat patients with potential rectal STIs according to current guidelines.8 An alternative specimen collection approach would be for clinicians to have patients who are NAAT positive for gonorrhea return to a clinic to have an extragenital culture done. This approach reduces needless testing by limiting testing to patients with confirmed positive test results; the limitation is that it requires a second clinical visit for patients who are positive. If treatment of a symptomatic patient had been withheld at the initial visit for some reason, then this second visit is required. A third option is to only perform NAAT, but this limits data collection about drug resistance.
A second consideration relates to swab selection for test-of-cure. Although NAAT is acceptable, extragenital culture may be considered a first option because of the low rate of true treatment failures and the fact that the test is 100% specific.14 When deciding which test to use, it is important to remember that NAAT can produce false-positive results up to 4 weeks after chlamydia treatment and up to 3 weeks after gonorrhea treatment.14 This occurs because NAAT detects DNA material, which does not necessarily signal viable organisms. After successful treatment, some of this genetic material may remain in situ for a few weeks. In these cases, positive results may indicate treatment failure, reinfection, or simply premature retesting of a successfully treated infection; NAAT, however, cannot distinguish between these outcomes. For these reasons, Public Health Ontario recommends culture as first-line for test-of-cure.14 See Pharyngeal testing flow and Rectal testing flow for detailed pathways for swab selection.
In summary, the recommended approach for screening for chlamydia and gonorrhea is to perform NAAT for anyone who, based on clinical judgment, could be “high risk” for these infections, and when gonorrhea and/or chlamydia pretest probabilities are elevated (based on group prevalence), as is common for persons who are sexual contacts of individuals diagnosed with either of these infections, MSM, and sex trade workers and their clients. Otherwise, consider performing culture when screening lower-risk patients for chlamydia and gonorrhea, although NAAT could be appropriate because of its higher sensitivity. Culture is also appropriate when a patient's clinical presentation could be gonorrhea, but the use of culture in this situation would be to determine antibiotic susceptibility, not diagnosis. Lastly, culture is also the first-line approach for tests-of-cure, although NAAT can be performed if sufficient time has passed since treatment. If done too soon, NAAT can yield positive results based on nonviable organisms. As such, NAAT or culture can be performed, with each test having factors that make it preferable.
This section discusses how to perform extragenital testing. For pharyngeal swabs, evidence highlights the need to press the swab firmly against both palatine tonsils and the posterior oropharynx to induce the gag reflex.25,26 In one study, clinicians who performed swabs using this technique had higher positivity rates, compared with those who did not.25 A second study involving the same staff had all providers implement the swabbing technique that yielded superior detection outcomes in the first study; the authors identified an overall increase in positivity rates among those not previously performing swabs this way.27 For rectal swabs, the described technique is to insert the swab past the internal anal sphincter to sample the mucosa, avoiding fecal contamination.28 Matching the recommended approach for using these swabs for endocervical specimen collection, the swab should be left in place for 10 to 15 seconds to ensure adequate swab exposure. Clinicians should also discard swabs that are visibly soiled with fecal matter and repeat the process with a new swab. In patients with rectal symptoms, clinicians could consider performing specimen collection using an anoscope.29 This technique facilitates direct sampling of visible discharge, and allows inspection of mucosa, which may show edema, erythema, and/or ulceration in the case of herpes simplex virus or LGV.29 Anoscopy, however, is not required, and a blind swab is acceptable for specimen collection.
Recommended screening approach summary
In Canada, the latest clinical guidelines recommend performing NAAT and an extragenital culture on patients with rectal symptoms.8,14 For those without symptoms, clinicians should perform NAAT for the patients Public Health Ontario defines as high-risk, and an extragenital culture for those defined as low-risk, with the possibility of doing a NAAT based on clinical presentation and judgment.14 Because of the possibility of false-positive results after treatment for chlamydia and gonorrhea, clinicians perform test-of-cure according to guidelines using extragenital culture or delay such testing until 3 to 4 weeks from treatment. This approach helps ensure appropriate testing while minimizing false-positive test results; it also generates data about antimicrobial resistance for gonorrhea. This clinical strategy is easily adopted in primary care practice and may help identify many asymptomatic infections.
3. Choudhri Y, Miller J, Sandhu J, Leon A, Aho J. Gonorrhea
in Canada, 2010-2015. Can Commun Dis Rep
4. Choudhri Y, Miller J, Sandhu J, Leon A, Aho J. Chlamydia
in Canada, 2010-2015. Can Commun Dis Rep
9. Workowski KA, Bolan GACenters for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep
10. Stamm WE. Chlamydia trachomatis
infections of the adult. In: Holmes KK, Sparling PF, Stamm WE, et al., eds. Sexually Transmitted Diseases
. 4th ed. New York, NY: The McGraw Hill Companies; 2008:575–594.
11. O'Byrne P, MacPherson P, Ember A, Grayson MO, Bourgault A. Overview of a gay men's STI/HIV testing clinic in Ottawa: clinical operations and outcomes. Can J Public Health
12. O'Byrne P, MacPherson P, DeLaplante S, Metz G, Bourgault A. Approach to lymphogranuloma venereum. Can Fam Physician
13. Hook EW, Handsfield HH. Gonococcal infections in the adult. In: Holmes KK, Sparling PF, Stamm WE, et al., eds. Sexually Transmitted Diseases
. 4th ed. New York, NY: The McGraw Hill Companies; 2008:627–346.
15. Gradison M. Pelvic inflammatory disease. Am Fam Physician
16. McConaghy JR, Panchal B. Epididymitis: an overview. Am Fam Physician
17. Mayor MT, Roett MA, Uduhiri KA. Diagnosis and management of gonococcal infections. Am Fam Physician
18. Mishori R, McClaskey EL, WinklerPrins VJ. Chlamydia trachomatis
infections: screening, diagnosis, and management. Am Fam Physician
19. Selmi C, Gershwin ME. Diagnosis and classification of reactive arthritis. Autoimmun Rev
21. Ota KV, Tamari IE, Smieja M, et al Detection of Neisseria gonorrhoeae
and Chlamydia trachomatis
in pharyngeal and rectal specimens using the BD Probetec ET system, the Gen-Probe Aptima Combo 2 assay and culture. Sex Transm Infect
22. Akobeng AK. Understanding diagnostic tests 1: sensitivity, specificity and predictive values. Acta Paediatr
25. Razali MF, Fairley CK, Hocking J, Bradshaw CS, Chen MY. Sampling technique and detection rates for pharyngeal gonorrhea
using culture. Sex Transm Dis
26. Bissessor M, Whiley DM, Lee DM, et al Detection of Neisseria gonorrhoeae
isolates from tonsils and posterior oropharynx. J Clin Microbiol
27. Mitchell M, Rane V, Fairley CK, et al Sampling technique is important for optimal isolation of pharyngeal gonorrhoea. Sex Transm Infect
28. Jarvis C, Browne AJ, MacDonald-Jenkins J, Luctkar-Flude M. Physical Examination and Health Assessment
. 2nd ed. Toronto: Elsevier; 2014.