Approach to sexually transmitted infection testing for men who have sex with men

Case description

A 34-year-old male patient requests testing for STIs. He reports 5 days of mild diarrhea with cramps and an incomplete sensation of evacuation. He has noted some blood when wiping. These symptoms started 2 days after his most recent sexual contact, which occurred during a visit to Ottawa, Ont. The patient reports having felt feverish for a few days. The review of systems is otherwise unremarkable, and the patient has no relevant past medical history.

   The patient’s most recent sexual contact was with a man who reported being HIV positive with an undetectable viral load. The patient knows nothing further about this partner. This encounter involved oral sex with oral-genital and oral-anal contact (given and received) and receptive anal sex. Condoms were not used. He reports that his penultimate sexual contact with someone different occurred 10 days before symptom onset and involved receptive anal sex.

   On examination the patient’s anal verge is erythematous. There are no lesions, discharge, or blood and no papules, pustules, ulcers, or chancres. The digital rectal examination does not reveal any masses, tenderness, or blood. Findings of examinations of the skin, oropharynx, cervical lymph nodes, genitals, and inguinal lymph nodes are unremarkable. The patient has proctocolitis and testing for infections outlined in Table 1 is warranted to determine the cause of his symptoms.^1,3-8

Sources of information

We reviewed guidelines from the Public Health Agency of Canada,^1,8 the US Centers for Disease Control and Prevention (CDC),³ the Ontario Ministry of Health,⁴ Health Canada,^5,6 and Public Health Ontario.^7,9

Main message

Testing for gonorrhea and chlamydia. Between 2011 and 2019 rates of gonorrhea and chlamydia infections in Canada increased by 171% and 26%, respectively,¹⁰ followed by decreases in 2020, likely due to decreased testing during the COVID-19 pandemic¹⁰ rather than decreases in transmission. When testing MSM for gonorrhea and chlamydia, remember that most infections are identified in the pharynx and rectum. One study from Ottawa found 70% of gonorrhea and 65% of chlamydia infections in MSM were exclusively extragenital.¹¹ If practitioners order only urine testing, for every 3 gonorrhea infections identified, 7 would be missed.¹¹

Gonorrhea and chlamydia testing should be done by nucleic acid amplification testing (NAAT), ruling out infection if results are negative. For cisgender MSM, first-catch urine specimens are recommended.⁹ For asymptomatic transgender MSM with internal genitals (eg, vaginas, neovaginas, front holes), urine testing is noninferior to self- and clinician-collected swabs.⁹ Symptomatic transgender MSM should undergo physical examination with clinician-collected specimens. Extragenital (pharynx and rectum) testing is indicated for all MSM.^1,3,9 With proper instructions, patients can self-collect pharyngeal and rectal swabs with sensitivity results equal to those of clinician-collected swabs.¹² Rectal specimens that are positive for chlamydia should undergo additional polymerase chain reaction (PCR) testing to rule out lymphogranuloma venereum. Chlamydia subtyping should also occur when patients present with suggestive symptoms,¹ including genital ulcerations or inguinal buboes. Patients with any PCR-based specimen that is positive for gonorrhea should be recalled for repeat testing by culture. This can be done at the time of treatment. Due to increasing rates of drug-resistant gonorrhea seen internationally,¹³ collecting cultures and obtaining antimicrobial sensitivity data is prudent. Treated patients should return in 4 to 7 days for repeat testing as test of cure by culture. The US CDC suggests testing MSM every 3 to 6 months for gonorrhea and chlamydia.³

Testing for syphilis. Between 2011 and 2019 the incidence of infectious syphilis increased by 389% in Canada, with ongoing increases noted during the COVID-19 pandemic despite reduced testing.¹⁰ Consistently, gay and bisexual men and other MSM account for most new diagnoses, although rates in recent years have been increasing among those who identify as heterosexual males and females with corresponding increases in congenital infections.¹⁴

Testing is done primarily via blood. Patients with a chancre may present prior to seroconversion and have a negative blood test result (sensitivity is 75% in the primary stage).¹⁵ In such instances, testing should be repeated in 2 to 4 weeks to rule out infection. If there is clinical suspicion of syphilis, empirical treatment with 2.4 million units of benzathine penicillin G given intramuscularly should not be withheld while awaiting results; patients who are allergic to β-lactam medications can be prescribed 100 mg tablets of doxycycline taken orally twice daily for 14 days.¹ Patients with secondary syphilis (systemic symptoms such as rash, lymphadenopathy, and fever) will have a positive test result at presentation. Clinicians should bear in mind that once a patient has positive test results, the syphilis screen result remains positive for life. Serology will therefore identify historical infections. Repeat infections and response to treatment are based on changes in the rapid plasma reagin titre.^1,3,15 Patients who are contacts of people who are newly diagnosed with infectious syphilis should receive empirical treatment and have serology testing done at presentation (irrespective of timing since sexual contacts) and repeated 4 weeks after the contact of concern, if results are negative.^1,3,15 Although not routinely available, syphilis testing can involve direct testing of material from lesions (eg, direct fluorescent antibody testing, PCR), which can identify some primary infections before seroconversion,^1,3 but this can be performed only if lesions are present.^3,15 Interpretation of syphilis test results can be facilitated using a 2019 publication that 2 authors of this article (P.O.B. and P.M.) published in BMJ.¹⁵ Although no clear evidence guides screening recommendations, Canadian and US guidelines advise MSM who are sexually active with more than 1 partner to be tested for syphilis every 3 to 6 months.^1,3

Testing for herpes simplex virus (HSV). Herpes simplex virus, while often sexually transmitted, is not a reportable infection in all provinces and territories,¹ and therefore data on incidence and prevalence are not available. Using data from 2009 to 2011, researchers estimated the prevalence of HSV among Canadian adults to be 13.6%.¹⁶

Testing for HSV is used to confirm or rule out diagnosis in patients with suggestive anogenital lesions. Most commonly, HSV is identified by NAAT or viral culture.^1,3 A swab should be taken of an active lesion (unroofed vesicle or ulcer). Test sensitivity of viral cultures varies depending on duration of infection and type of lesion being sampled, ranging from 94% for vesicles to 87% for pustular lesions to 70% for ulcers.¹ Samples from healing or dried lesions are less likely to have positive results. Nucleic acid amplification testing is increasingly used for diagnosis and has sensitivity and specificity of 100%.¹ Blood tests have no role in the diagnosis of HSV.

Testing for HIV. The rate of HIV diagnoses in Canada remained fairly stable between 2011 and 2020, and MSM continue to account for nearly half of incident infections.¹⁷ Among MSM, those with ongoing risk factors for HIV acquisition should be offered HIV preexposure prophylaxis (PrEP) (Table 2).¹⁸ In a study conducted in Kenya and Uganda involving HIV-serodiscordant male and female couples, providing PrEP to uninfected partners was associated with a 96% reduction in HIV incidence¹⁹; cumulative evidence indicates this reduction is greater than 99%. A study conducted in Ottawa suggests the use of PrEP may help curb the number and rate of new HIV diagnoses at the population level.²⁰

For patients presenting after known or possible exposure to HIV, testing should be done at presentation and repeated at 3 weeks and 6 weeks after exposure.⁴ Patients who present within 72 hours of exposure should be referred to a local emergency department for consideration of post-exposure prophylaxis (PEP). Fourth-generation antigen and antibody tests can rule in new infections as early as 17 days from acquisition and rule out infection after 6 weeks.⁴ Third-generation antibody tests, including point-of-care tests, have a testing window period of 12 weeks.⁴ Patients presenting with seroconversion-like symptoms (ie, mononucleosis-like) or chronic infection (eg, chronic weight loss, persistent nontender lymphadenopathy, recurrent thrush) should also be tested.^1,3,4 Ontario testing guidelines recommend annual testing for MSM “even when they report consistently using risk reduction practices—as gaps in protection may occur.”⁴ Testing for HIV is recommended every 3 months for MSM who report recurring condomless sex with more than 1 partner.

In 2020 Health Canada approved HIV self-testing.²¹ Self-tests can be purchased from the manufacturer or from pharmacies, or they can be obtained for free from GetaKit (https://getakit.ca), a project led by 2 of the authors of this article (P.O.B. and L.O.) at the University of Ottawa, which provides such self-tests to persons with risk factors across Ontario.²² In 2023 Health Canada approved a point-of-care combination syphilis and HIV test with an overall sensitivity of 76.7% and specificity of 99.8%.^23-25 The sensitivity of this point-of-care test for syphilis drops to 28.4% for persons with nonreactive rapid plasma reagin results, signalling that this test cannot rule out early or late infections.²⁵ This test is also only a screen and cannot be used in persons with prior syphilis infections, as these antibodies persist after a first infection. While this test may be useful in outreach settings or when follow-up is challenging, the performance limitations of this device hinder its usefulness in clinical settings and may provide a false sense of security in people at higher risk. Serology testing should always be used in conjunction with this point-of-care device.

Testing for mpox. In May 2022 a global mpox outbreak occurred, and more than 1500 diagnoses have been made in Canada since then; 1255 (83%) of these infections were recorded in Ontario and Quebec.²⁶ Nearly all cases were among MSM and, uniquely, this outbreak was associated with sexual transmission.^5,26

For patients with a rash or lesions, a direct swab of the lesions, lesion fluid, or material (crust, scab) is recommended.²⁷ Considering the high viral concentration in these specimens and test sensitivity of approximately 90%,²⁷ other mpox testing methods are not indicated when skin lesions are present. For lesions in the oral cavity, throat, anus, or rectum, swabs of the nasopharynx and rectum are recommended. In patients in whom mpox is suspected (eg, contacts, prodromal symptoms) but skin lesions are not evident and in patients for whom adequate samples cannot be obtained from skin lesions, a nasopharyngeal or throat swab and blood test are recommended.²⁷ While these tests may be less sensitive than lesion swabs (ie, 60% to 70% for nasopharyngeal test, 40% to 50% for blood test),²⁷ they may help identify patients with asymptomatic mpox infections.

Testing for enteric bacteria and protozoa. Outbreaks of Shigella infection (shigellosis) among MSM have been reported with approximately 50% of isolates having antibiotic resistance and increasing numbers being extensively drug resistant.^28,29 While antibiotics can reduce symptom course and severity, shigellosis usually resolves without treatment within 5 to 7 days.^6,28,29 Antibiotics are usually recommended only for severe disease, including for bacteremia. The primary testing method for Shigella and other enteric bacteria (Table 1)^1,3-8 is stool culture from patient-collected samples.²⁹ Patients should be given vials containing stool transport media and instructed to add fresh stool to the vial. Antimicrobial resistance testing is conducted on specimens with positive test results²⁸ and is important to ensuring adequate therapeutic coverage, if treatment is indicated.

Giardia species are enteric protozoa transmitted through contaminated food and water and by oral-anal contact.^8,30 Symptoms include diarrhea with steatorrhea, abdominal cramps and bloating, flatulence, nausea, and malaise.^8,30 Cryptosporidium species can cause diarrhea, ranging from scant to voluminous, with associated nausea and crampy abdominal pain.⁸ Testing for intestinal protozoa is by direct microscopic examination, although NAAT is becoming common. Patients should be provided with vials containing ova and parasite transport media and instructed to add fresh stool to the vial. In low-prevalence settings at least 2 or 3 separate samples should be collected.³¹

For all enteric infections, testing is indicated only when symptoms are present.

Case resolution

Laboratory test results were received confirming the diagnoses of non–lymphogranuloma venereum rectal chlamydia and shigellosis. Results were negative for rectal gonorrhea, pharyngeal chlamydia, and gonorrhea; HIV, syphilis, and mpox serology; HSV and rectal mpox PCR; and enteric and protozoan stool samples. The patient was treated for rectal chlamydia with 100 mg of oral doxycycline twice daily for 7 days¹ and counselled on hydration and shigellosis symptom monitoring. The patient was initiated on PrEP and advised to continue monitoring per guidelines.¹⁸ We also offered doxycycline PEP, which consists of a single 200 mg dose, preferably within 24 hours but not more than 72 hours after sex; this intervention has been shown in 2 US studies^32,33 to reduce the risk of chlamydia and syphilis infection by about 70%; the effect on gonorrhea varied, possibly due to local resistance patterns. The US CDC recommends doxycycline PEP for MSM who have been diagnosed with an STI within the preceding 12 months.³⁴ See Tables 3 and 4 for a summary of recommendations.^{1,3-7,15,18,27,33}