Extra-Genital Chlamydia and Gonorrhea Infections

By John Papp, PhD

Chlamydia and gonorrhea infections are common in non-genital sites in some populations such as men who have sex with men (MSM). Be-cause extra-genital infections are common in MSM and most infections are asymptomatic1, routine annual screening of extra-genital sites in MSM is recommended. No recommendations exist regarding routine extra-genital screening in women as studies have focused on genitourinary screening, but rectal and oropharyngeal infections are not uncommon.

In 2003, Kent and colleagues1 performed the first large study looking at NAATs for diagnosing chlamydia and gonorrhea infections in multiple anatomic sites in MSMs. They used Becton Dickinson’s ProbeTec NAAT which they had previously validated for such use. Among 6,434 MSM attending an STD clinic or a gay men’s clinic, they found the prevalence by site for chlamydia was 7.9% for the rectum, 5.2% urethral, and 1.4% pharyngeal, and prevalence by site for gonorrhea was 6.9% for the rectum, 6% urethral,and 9.2% pharyngeal. Most (84%) of the rectal gonorrhea and chlamydia infections were asymptomatic. A point of particular importance was that 53% of chlamydia and 64% of gonorrhea infections were at non-urethral sites and would have been missed if the traditional approach to screen-ing of men by testing only urethral specimens had been used.

The scope of the problem of extra-genital infection in MSM is not known at the national level. The Centers for Disease Control and Prevention (CDC) coordinated an evaluation of MSM attending several community based organizations and public or STD clinics in 2007 and found that of approximately 30,000 tests performed, 5.4% were positive for rectal gonorrhea and 8.9% for rectal chlamydia2. Pharyngeal gonorrhea tests were positive at 5.3%, and 1.6% were positive for chlamydia.

In the United Kingdom, some studies on screening MSMs have been performed using NAATs, and in one study of 3,076 MSM attending an STD clinic there was an 8.2% prevalence of chlamydia infection in the rectum and 5.4% in the urethra. The majority (69%) of the men with chlamyydia were asymptomatic, stressing the need for screening3.

Schachter et al4 compared culture to two NAATs (Gen-Probe’s Aptima Combo2 (AC2) and Becton Dickinson’s ProbeTec) for the detection of chlamydia and gonorrhea in pharyngeal and rectal specimens collected from 1,110 MSM being seen in an STD clinic. All NAAT positive results were con-firmed when the original test and a test using alternate primers were positive. In this particular study, Roche’s Amplicor test was excluded because of specificity for gonorrhea with oropharyngeal swabs being only 78.9%.

For oropharyngeal gonorrhea sensitivities were 41% for culture, 72% for SDA and 84% for AC2, and for rectal gonorrhea, sensitivities were 43% for culture, 78% for SDA and 93% for AC2. For oropharyngeal infections with chlamydia (only 9 infections detected), sensitivities were 44% for culture, 67% for SDA and 100% for AC2, and for rectal chlamydia, sensitivities were 27% for culture, 63% for SDA and 93% for AC2. Specificities were greater than 99.4% for all specimens, tests and anatomic sites. It is clear from this study that the number of infections detected was more than double when a more sensitive NAAT was used, as compared to the use of standard culture. Other re-searchers have also demonstrated the superiority of NAATs as compared to culture for diagnosing chlamydia and gonorrhea in rectal and oropharyngeal sites5,6,7.

Culture is less sensitive for detecting chlamydia and gonorrhea at extra-genital sites. While NAATs are clearly the better choice for testing extra-genital site specimens, they have not been cleared by the FDA for the detection of chlamydia or gonorrhea infections of the rectum and oropharynx. Results from these tests may be used for patient management if the laboratory has satisfied CMS regulations for CLIA compliance for test modification (CFR493.1253(b)(2)). Many laboratories across the nation have met CMS regulations for off-label testing with commercial NAATs and can offer expanded testing services to clinicians assessing patients for extra-genital chlamydia and gonorrhea infections.

Some NAATs that have been shown to detect commensal Neisseria species in urogenital specimens may have comparable low specificity when testing oropharyngeal specimens for gonorrhea. Thus a NAAT that does not react with non-gonococcal commensal Neisseria species is recommended when testing oropharyngeal specimens for gonorrhea.

References

  1. Kent CK, Chaw JK, Wong W, Liska S, Gibson S, Hubbard G, Klausner JD. Prevalence of rectal, urethral, and pharyngeal chlamydia and gonorrhea detected in 2 clinical settings among men who have sex with men: San Francisco, California, 2003. Clin Infect Dis. 2005; 41;67-74.
  2. Centers for Disease Control and Prevention. Clinic-based testing for rectal and pharyngeal Neisseria gonorrhoeae and Chlamydia trachomatis infections by community-based organizations – five cities, United States, 2007. MMWR 2009;58;716–9.
  3. Annan NT, Sullivan AK, Nori A, Naydenova P, Alexander S, McKenna A, Azadain B, Mandalia S, Rossi M, Ward H, Nwokolo N. Rectal chlamydia–a reservoir of undiagnosed infection in men who have sex with men. Sex Transm Infect 2009;85:176–9.
  4. Schachter J, Moncada J, Liska S, Shayevich C, Klausner JD. Nucleic acid amplification tests in the diagnosis of chla-mydial and gonococcal infections of the oropharynx and rectum in men who have sex with men. Sex Trans Dis 2008;35:637–42.
  5. Schachter J. DFA, EIA, PCR, LCR and other technologies: what tests should be used for diagnosis of chlamydia infections? Immunol Invest 1997;26:157–61.
  6. Bachmann LH, Johnson RE, Cheng H, Markowitz LE, Papp JR, Hook III EW. Nucleic acid amplification tests for diagnosis of Neisseria gonorrhoeae oropharyngeal infections. J Clin Microbiol 2009;47:902–7.
  7. Bachmann LH, Johnson RE, Cheng H, Markowitz LE, Papp JR, Palella FJ, Hook III EW. Nucleic acid amplifica-tion tests for diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis rectal infections. J Clin Microbiol 2010;48:1827–32.