Lymphogranuloma Venereum Is Rare in Australian Community-Based Samples of Men Who Have Sex With Men

Abstract

Lymphogranuloma venereum (LGV) typing was performed on chlamydia-positive samples obtained in Sydney, Australia, between 2005 and 2007, from community-based cohorts of predominantly asymptomatic HIV-infected and -uninfected men who have sex with men. The number of chlamydia tests and follow-up for each cohort were as follows: 2082 (90.2% of eligible visits) over 2005.1 person-years (PY) of follow-up in the HIV-uninfected cohort; and 521 (70.8% of eligible visits) over 320.2 PY of follow-up in the HIV-infected cohort. One case of rectal LGV in a symptomatic HIV-infected participant was identified among 64 Chlamydia trachomatis infections, giving an LGV incidence in the HIV-infected cohort of 0.3 per 100 PY, 95% Confidence Interval 0.008–1.7. Routine LGV typing of chlamydia infections in asymptomatic Australian men who have sex with men does not appear justified.

In Brief

Routine lymphogranuloma venereum typing of chlamydia infections in asymptomatic men who have sex with men does not appear justified based on findings from a large Australian community-based sample.

Lymphogranuloma venereum (LGV) has reestablished itself as an important sexually transmitted infection (STI) among men who have sex with men (MSM) in large US and European cities.¹ Several rectal LGV cases have also been reported in Australia.^2–5 In common with most reports worldwide, these cases predominantly comprised HIV-infected MSM with symptoms of proctitis attending clinical services.

Previous investigations in North America and the United Kingdom failed to identify a substantial reservoir of subclinical LGV infection among MSM.^6–8 However, these studies were predominantly in clinic-based samples. To our knowledge, there are no published estimates of the prevalence of LGV among MSM in the community. To investigate whether there is an asymptomatic pool of LGV in the community, we performed LGV typing on all Chlamydia trachomatis Deoxyribonucleic acid (DNA)-positive specimens identified in 2 community-based cohort studies of HIV-infected and -uninfected MSM in Sydney, Australia.

The methods of the Health in Men (HIM) HIV-uninfected cohort and the Positive Health (pH) HIV-infected cohort studies have previously been published.⁹ Ethics approval was obtained from the University of New South Wales. In each study, the men underwent annual face-to-face interviews in which detailed behavioral and symptom data were sought. Routine questioning of anal symptoms included recent and current presence of discharge, itch, sores, bleeding, tearing, and pain on defecation.

Comprehensive STI screening was offered annually to participants in both cohorts.⁹ In consenting participants, C. trachomatis and N. gonorrhoeae testing of urine, pharyngeal swabs, and self-collected anal swabs was performed by strand displacement amplification (SDA) (BD ProbeTec, BD Diagnostics, Sparks, MD, USA). Serovar analysis was performed on all pharyngeal and anogenital samples positive for C. trachomatis DNA from January 2005 until study completion in mid-2007. Serovar analysis of C. trachomatis involved DNA sequencing across all 4 variable domains of the ompA gene encoding for the immunodominant major outer membrane protein, as described previously.¹⁰

In the HIV-uninfected and HIV-infected cohort, a total of 2082 (90.2% of eligible visits) and 521 (70.8% of eligible visits) SDA chlamydia tests, respectively, were performed. The total follow-up time was 2005.1 person-years (PY) in the HIV-uninfected cohort and 320.2 PY in the HIV-infected cohort. Participants in both cohorts were predominantly asymptomatic. Any anal symptom was reported by participants at 2.6% (95% CI: 2.2%–3.1%) and 3.7% (95% CI: 2.7%–4.9%) of study visits in the HIV-uninfected and HIV-infected cohorts, respectively.

Among participants in the HIV-uninfected cohort, C. trachomatis was identified on 34 anal (positivity rate, 1.63%; 95% CI: 1.13%–2.27%), 9 urine (positivity rate, 0.43%; 95% CI: 0.20%–0.81%), and 3 pharyngeal (positivity rate, 0.14%, 95% CI: 0.003%–0.42%) samples. Serovar analysis revealed no LGV among these 46 positive chlamydia samples. Among participants in the HIV-infected cohort, chlamydia infection was identified on 13 anal (positivity rate, 2.50%; 95% CI: 1.34%–4.22%), 3 urine (positivity rate, 0.58%; 95% CI: 0.12%–1.67%), and 2 pharyngeal (positivity rate, 0.38%; 95% CI: 0.05%–1.38%) samples. All positive C. trachomatis samples detected on the SDA assay were also positive for chlamydia DNA on the ompA assay. Only 1 of 18 HIV-infected participants diagnosed with C. trachomatis was infected with an LGV serovar (LGV incidence in the HIV-infected cohort 0.3 per 100 PY, 95% CI: 0.008–1.7). The sample, collected in 2005, was an anal swab identified as L2b positive. The LGV-infected participant was 44 years old, reported receptive unprotected anal intercourse with other HIV-infected men in the previous 6 months, and reported mild anal “tearing” on the day of the interview. As per study protocol, the LGV-infected participant was referred to his usual doctor for treatment. Data were not sought in either cohort regarding treatment regimens prescribed by participants' doctors. Nonetheless, anal screening performed the following year as part of the pH study was negative for C. trachomatis.

The majority of participants from both cohorts were recruited at gay community events, and less than 4% were from clinics. Therefore, we believe participants to be broadly representative of gay-community–attached MSM in Sydney.

Outside Australia, LGV appears to be most common in a well-defined sexually adventurous subpopulation of HIV-infected MSM.¹ If a representative sample of such men had not been recruited into our cohorts, it is possible that we might have underestimated the prevalence of LGV in the Sydney gay community. Another possible limitation of our analysis is that serovar analysis was only performed on swabs initially testing positive for C. trachomatis on the SDA test. This assay may be less sensitive than other nucleic acid amplification tests for anorectal C. trachomatis detection among MSM.¹¹ Our previous analysis from the HIV negative HIM cohort found pharyngeal chlamydia to be rare in MSM.¹² However, nucleic acid amplification tests have not been validated for diagnosis of chlamydia in the pharynx. Thus, some anal and pharyngeal chlamydia infections may have initially been missed and therefore not referred for serovar analysis.

HIV-infected MSM are disproportionately affected by a range of STIs⁹ including LGV.¹³ However, we detected relatively few chlamydia infections in our community-based HIV-infected cohort. This may be attributed to frequent STI screening, detection, and treatment performed by their HIV physicians during regular visits for routine HIV care, as has been recommended for Australian HIV-infected MSM.⁹

Dutch investigators¹³ have reported a high proportion of asymptomatic anorectal LGV, which contrasts sharply with reports from Australia^2–5 and other settings.^6,8 No history of recent overseas travel was sought from study participants in either cohort. It is possible that asymptomatic LGV may be detected more frequently in such high LGV prevalence settings as a result of screening MSM during the “presymptomatic” phase.¹ Nonetheless, the lack of LGV identified among predominantly asymptomatic MSM in a setting in which clinical cases of LGV have been described^2,5 suggests that most LGV in Australian MSM is symptomatic.

To confirm this hypothesis, further community-based studies are required in settings in which clinical LGV is more common among MSM. Our findings concur with those among large clinical samples of MSM⁶ and suggest that routine LGV typing of chlamydia infections in asymptomatic Australian MSM is not justified at this stage.