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Rectal chlamydia—a reservoir of undiagnosed infection in men who have sex with men
  1. N T Annan1,
  2. A K Sullivan1,
  3. A Nori1,
  4. P Naydenova1,
  5. S Alexander2,
  6. A McKenna1,
  7. B Azadian1,
  8. S Mandalia1,
  9. M Rossi1,
  10. H Ward2,3,
  11. N Nwokolo1
  1. 1
    GUM/HIV Directorate, Chelsea & Westminster Hospital NHS Foundation Trust, London, UK
  2. 2
    Health Protection Agency, Centre for Infections, London, UK
  3. 3
    Imperial College, London, UK
  1. Dr Naa Torshie Annan, Genitourinary Medicine Clinic, Frimley Park Hospital NHS Foundation Trust, Portsmouth Road, Camberley, GU16 7UJ, UK; torshie.annan{at}fph-tr.nhs.uk

Abstract

Objective: To determine the prevalence of rectal chlamydia infection in a cohort of men who have sex with men (MSM) and the proportion of infection that would be missed without routine screening.

Methods: MSM presenting to four HIV/GUM outpatient clinics at the Chelsea & Westminster Hospital NHS Foundation Trust between 1 November 2005 and 29 September 2006 were offered testing for rectal chlamydia infection in addition to their routine screen for sexually transmitted infections (STIs). Chlamydia trachomatis (CT) tests were performed using the Beckton-Dickinson Probe-Tec Strand Displacement Assay. Positive samples were re-tested at the Sexually Transmitted Bacteria Reference Laboratory, to confirm the result and identify lymphogranuloma venereum (LGV)-associated serovars.

Results: A total of 3076 men were screened. We found an 8.2% prevalence of infection with CT (LGV and non-LGV serovars) in the rectum and 5.4% in the urethra. The HIV and rectal chlamydia co-infection rate was 38.1%. The majority of rectal infections (69.2%, (171/247)) were asymptomatic and would have been missed if routine screening had not been undertaken. Of the samples re-tested, 94.2% (227/242) rectal and 91.8% (79/86) urethral specimens were confirmed CT positive and 36 cases of LGV were identified.

Conclusion: Our data show a high rate of rectal chlamydia infection, in the majority of cases it was asymptomatic. We recommend routine screening for rectal chlamydia in men at risk, as this may represent an important reservoir for the onward transmission of infection.

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Genital chlamydia is the most common bacterial sexually transmitted infections (STI) diagnosed within genitourinary medicine (GUM) clinics in the United Kingdom.1 2 Currently, testing for urethral chlamydia infection is routinely offered to all men presenting to GUM clinics for sexual health screening. Rectal chlamydia testing in men who have sex with men (MSM) is not routinely offered in the majority of clinics,3 neither is it recommended in the British Association for Sexual Health and HIV (BASHH) guidelines for STI screening.4

Studies from the UK5 6 and North America7 8 have reported prevalence rates of rectal chlamydia between 7.2% and 8.5%, with high rates of asymptomatic infection (52%–86%). Like other STIs that cause a breach in the genital mucosa,911 genital chlamydia facilitates the acquisition and transmission of HIV.12 13 Although there are currently no data to suggest rectal chlamydia infection has a similar effect on transmission of HIV, it is certainly feasible. Screening and early treatment may therefore impact on the onward transmission of HIV infection.

The resurgence of LGV in Western Europe1417 has seen many cases diagnosed within the UK,18 19 with a significant number of cases from our centre. As a direct result of the numbers diagnosed, we began offering routine screening for infection with rectal chlamydia in MSM in November 2005. We were subsequently involved in the case finding exercise for lymphogranuloma venereum (LGV) initiated by the Health Protection Agency, data from which is presented by Ward et al.20

The objectives of this study were to determine: (1) the prevalence of rectal chlamydia infection in an MSM cohort, (2) the proportion of asymptomatic infections, and (3) the number of infections that would be missed if routine rectal screening had not been performed.

METHODS

All MSM who presented to the directorate’s four HIV/GUM outpatient clinics at the Chelsea & Westminster Hospital NHS Foundation Trust were screened for rectal chlamydia infection if they had a history of receptive anal intercourse. The study period was for 11 months from November 2005. Ethics committee approval and individual patient consent were not obtained as this was considered to be implementation and evaluation of local clinic screening protocols linked to case note review. Information was collected from a database containing GUM attendances, demographic details and STI diagnoses based on the KC60 statistical returns system. Local clinic codes recorded in this database were also used to identify MSM. All case notes of MSM diagnosed with Chlamydia trachomatis (CT) during this period were reviewed and data on symptoms, concurrent STIs, results of rectal microscopy and treatment were collected retrospectively.

Screening men for urethral chlamydia is routinely offered in our clinics using the Beckton-Dickinson Probe-Tec Strand Displacement Assay (B-D Probetec SDA) of a urethral swab specimen. We did not make any changes to this protocol during the study period. Laboratory tests for other STIs include urethral and rectal microscopy and culture for gonorrhoea, pharyngeal gonococcal culture and HIV antibody testing using the Abbott Determine Point-of-Care Antibody Test. Serological testing for syphilis (EIA IgG/M antibody, TPPA and VDRL) and hepatitis B (surface antigen, surface antibody and core antibody) are also offered as screening tests. For the purpose of this study, only men who presented for a full STI screen were included. We excluded individuals requesting HIV testing only or psychosexual counselling.

Screening was performed irrespective of rectal or urethral symptoms. Rectal symptoms were defined as any of the following: rectal discharge, pain or bleeding, diarrhoea, constipation, tenesmus or perianal ulceration. Urethral symptoms were urethral discharge, dysuria, frequency of micturition, irritation or an itching sensation in the urethra with or without evidence of inguinal lymphadenopathy.

Rectal and urethral chlamydia samples were taken using the standard female and male B-D Probetec swabs, respectively. The first sample taken was for microscopy and culture for Neisseria gonorrhoeae and the second for detection of Chlamydia trachomatis. Patients who reported rectal symptoms had samples taken under proctoscopic guidance and in asymptomatic men, swabs were inserted 1–2 cm into the anal canal without proctoscopy. Rectal microscopy was performed by highly skilled GUM-trained nursing staff for the presence of polymorphonuclear leucocytes (PMNL) and Gram-negative intracellular diplococci. For the purpose of the study a positive microscopy was defined as >10 PMNL per high power field. Other authors have reported an association between rectal LGV and greater than 10 PMNL on rectal microscopy.21 22

Positive samples were sent to the Sexually Transmitted Bacteria Reference Laboratory (STBRL) for confirmation of CT infection and identification of LGV serovars. From the outset all positive rectal samples were sent to the STBRL, as the validity of the B-D Probetec SDA for rectal sites had not been established. For logistical reasons, urethral samples were only sent in the last six months of the study, therefore only half were re-tested. A CT real-time polymerase chain reaction (PCR) assay developed by Centers for Disease Control and Prevention (CDC) was used to confirm that the sample was positive.23 Genotyping for LGV serovars was performed using the methods of Moore et al.24 Treatment for CT and LGV was prescribed as recommended in the BASHH guidelines.25 26

RESULTS

During the study period 3076 men were screened for STIs. The majority of men presenting for STI screening were white (82.5%) and the mean age was 35 years (median 32 years, range 16–81 years).

In total, 3017 rectal and 3076 urethral samples were tested for Chlamydia trachomatis infection. Fifty-nine men were not tested for rectal chlamydia as they did not report a history of receptive anal sex. Positive results were identified in 247 rectal and 165 urethral samples. The prevalence rates of STIs in the study population were rectal chlamydia 8.2% (247/3017), urethral chlamydia 5.4% (165/3076), rectal gonorrhoea 4.1% (125/3017), urethral gonorrhoea 4.6% (142/3076), pharyngeal gonorrhoea 1.3% (41/3076) and infectious syphilis 3.0% (91/3076).

Tables 1 and 2 summarise the demographics and clinical characteristics of the 397 men diagnosed with chlamydia; 62% (247/397) were diagnosed with rectal infection, 41.6% (165/397) had urethral infection and 3.8% (15/397) were diagnosed with chlamydia at both sites. Ten men re-presented with chlamydial infection eight weeks or more after treatment of the initial infection and, of these, seven were diagnosed with chlamydia at the same site (2/7 rectal and 5/7 urethral). All men with re-infection were treated with a single dose of azithromycin at the initial diagnosis except one with urethral chlamydia who was treated with a week’s course of doxycycline.

Table 1 Demographics of Chlamydia trachomatis-positive cases (LGV and non-LGV serovars)
Table 2 Concurrent STIs in men diagnosed with chlamydia (any site)

Most rectal chlamydia infection (all serovars) was asymptomatic (69.2% (171/247)) and would have been missed if screening was performed exclusively in symptomatic men. Only 8.2% (14/171) of asymptomatic men with rectal infection had concurrent urethral chlamydia infection. There were 14.2% (35/247) MSM diagnosed with rectal LGV and one with urethral LGV infection. Men diagnosed with rectal LGV were predominantly symptomatic (82.8%, (29/35)) as were those with urethral chlamydia infection (68.5%, (113/165)). The most common symptoms reported in men with rectal LGV infection were rectal discharge (60%), bleeding (34%) and pain (31%). In contrast, men diagnosed with non-LGV infection (47 men) reported rectal discharge (49%) and rectal discomfort or irritation (40%) as the predominant symptoms.

There was a high prevalence of other STIs; HIV, genital warts and gonorrhoea were the most common infections diagnosed (table 2). The HIV and rectal chlamydia co-infection rate was 38.1% (94/247), and 12.8% (12/94) were diagnosed with HIV and rectal chlamydia at the same visit. The rectal gonorrhoea and rectal chlamydia co-infection rate was 13.4% (33/247) and half (17/33) were symptomatic.

The majority of chlamydia-positive samples were sent to the STBRL for confirmation of CT23 and identification of LGV serovars.24 Five rectal samples were not re-tested; three had insufficient material and two were not sent because of human error. Urethral samples were sent for re-testing in the last six months of the study, therefore 52.1% (86/165) were available for re-testing. The results are summarised in table 3 and show 94.2% and 91.8% confirmatory rates for rectal and urethral chlamydia, respectively. All the nine rectal specimens that tested negative (STBRL) and four of six equivocal rectal specimens were obtained from asymptomatic men.

Table 3 Chlamydia samples: results of initial and confirmatory testing

The most common antibiotic prescribed for the treatment of non-LGV chlamydia was a single dose of 1 g azithromycin in 82.6% (328/397). Doxycycline 100 mg twice daily for 7 days was prescribed in 6.8% (27/397) and ofloxacin 400 mg daily for 7 days in 1.5% (6/397). Doxycycline 100 mg twice daily for 21 days was the treatment of choice for LGV (9.1% (36/397)).

In the univariable analysis (table 4), HIV infection (RR 2.53, 95% CI 1.56 to 4.08, p<0.001), rectal gonorrhoea (RR 5.37, 95% CI 1.86 to 15.51, p = 0.0002) and genital warts (RR 2.79, 95% CI 1.12 to 6.95, p = 0.016) were significantly associated with a diagnosis of rectal chlamydia infection. We repeated the analysis after excluding men diagnosed with LGV. The association between rectal chlamydia/HIV (RR 2.14, 95% CI 1.28 to 3.56, p = 0.004) and rectal chlamydia/rectal gonorrhoea (RR 5.53, 95% CI 1.90 to 16.10, p = 0.0002) was still statistically significant.

Table 4 Univariate logistic regression model showing the factors associated with rectal chlamydia infection

Men diagnosed with rectal chlamydia (all serovars) were significantly less likely to have urethral chlamydia infection (p<0.0001). The presence of PMNL on rectal microscopy (>10 PMNL per high power magnification) was not associated with rectal chlamydia (RR 1.16, 95% CI 0.68 to 2.00, p = 0.341). From table 4, 67.6% (50/74) MSM diagnosed with rectal chlamydia (all serovars) had a positive rectal microscopy; 95% (19/20) were diagnosed with LGV compared to 57.4% (31/54) diagnosed with non-LGV serovars.

DISCUSSION

Our data show an 8.2% prevalence rate of rectal chlamydia infection in MSM comparable to reports from other studies.58 20 27 Most rectal infection was asymptomatic (69.2%) and would not have been diagnosed if screening was undertaken exclusively in symptomatic men. Fourteen per cent of rectal chlamydia positive specimens were confirmed as LGV. The majority of LGV cases were symptomatic, consistent with reports from other centres in the UK.20

The rectal chlamydia infection rate (8.2%) was higher than rectal gonorrhoea infection (4.1%). Co-infection was found in 13.4%, similar to data from Whetham et al.27 Previously published data have also shown higher rates of rectal chlamydia in MSM.5 6 These studies used culture for identification of Neisseria gonorrhoeae but there is some evidence to suggest that nucleic acid amplification tests (NAATs) may be more sensitive than culture at extra genital sites.28 There is currently however no NAAT licensed for detection of gonorrhoea at extragenital sites and in clinical practice culture is the method of detection used.

Co-infections with other STIs were common and rectal chlamydia was significantly associated with HIV infection and rectal gonorrhoea. Men diagnosed with rectal chlamydia were significantly less likely to be diagnosed with urethral chlamydia and we found no association between a diagnosis of rectal chlamydia (all serovars) and a positive rectal microscopy. We found however a greater proportion of microscopy-positive men with rectal LGV infection, which has previously been reported by other authors.21 22 27

There has been concern about the validity of NAATs used to diagnose rectal chlamydia infection. Alexander et al29 have confirmed the C trachomatis status of positive rectal samples in 93.4% of B-D Probetec SDA, 87.5% of C trachomatis culture and 89.2% of Cobas Amplicor (Roche) samples using real-time PCR. Our data also show similar results when tested by the same group; 94.2% of positive rectal samples tested using the B-D Probetec SDA were confirmed positive with a real-time PCR.29 These and other studies30 show that high confirmatory rates can be achieved using NAATs to test for chlamydia at rectal sites.

In conclusion, our data show a higher rate of rectal chlamydia infection compared to gonorrhoea, a significant proportion of which was asymptomatic. Current STI guidelines in the UK only recommend routine screening for rectal gonorrhoea but not rectal chlamydia infection and our data supports the need to revisit these guidelines. We recommend routine screening for rectal chlamydia in MSM at risk of acquiring this infection.

Key messages

  • Our study shows higher rates of rectal chlamydia than rectal gonorrhoea and urethral chlamydia in men who have sex with men (MSM).

  • We have also shown that 94.2% of rectal samples tested using the Beckton-Dickinson Probetec Strand Displacement Assay can be confirmed by real-time polymerase chain reaction. We believe this is a reliable method for detection of rectal chlamydia.

  • Our findings strongly support screening MSM because of the high prevalence of asymptomatic infection with rectal Chlamydia trachomatis.

REFERENCES

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Footnotes

  • See Editorial, p 157

  • Competing interests: None.

  • Funding: None.

  • Contributors: NTA, AN, PN, AM and MR were involved in collecting and analysing the data. SA was involved in testing all the chlamydia positive specimens and genotyping for LGV serovars at the STBRL. BA is the lead microbiologist at our centre responsible for coordinating the testing of laboratory specimens and liaising with the STBRL. HW was responsible for initiating the case finding exercise in collaboration with the STBRL. SM specialised in the statistical analysis and NTA, AN, AS, HW and NN wrote the final manuscript.

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