Sexually Transmitted Diseases:
Gonorrhea Screening Among Men Who Have Sex With Men: Value of Multiple Anatomic Site Testing, San Diego, California, 1997–2003
Gunn, Robert A. MD, MPH*; O’Brien, Catherine J. MPH†; Lee, Marjorie A. MPH*; Gilchick, Robert A. MD, MPH*
From the *Public Health Services, Health and Human Services Agency, San Diego, California; and †Graduate School of Public Health, San Diego State University, San Diego, California
The authors thank Thomas A. Peterman, MD, MSc, Charlotte K. Kent, PhD, and Jeffrey D. Klausner, MD, MPH, for providing helpful comments and for Rita Perry for manuscript preparation.
Data were obtained from Public Health Services, Health and Human Services Agency, County of San Diego, CA.
Correspondence: Robert A. Gunn, MD, MPH, HIV, STD and Hepatitis Prevention Branch, M/S P505, 3851 Rosecrans Street, Suite 207, San Diego, CA 92110-3115. E-mail: email@example.com.
Received for publication January 16, 2008, and accepted March 27, 2008.
Background: The Centers for Disease Control and Prevention recommends that men who have sex with men (MSM) be screened annually for gonorrhea (GC) infection at the urethral, pharyngeal, or rectal site based on recent sexual exposure. This evaluation estimated the proportion of GC infections in MSM that would be missed if only urethral or urine specimens were tested.
Methods: Culture of specimens from all sites and urethral (or urine) nucleic acid amplification test (NAAT) results for gonorrhea were reviewed for all identified MSM attending the San Diego County STD Clinic during 1997–2003.
Results: During the 7-year period, 7333 MSM were tested for GC and 1157 (15.8%) had a positive test result at ≥1 sites. Overall, 10.8% of urethral, 9.8% of rectal, and 4.0% of pharyngeal tests were positive. Among 5812 patients who had a urethral and a rectal or pharyngeal specimen tested, 970 were positive and among those, 369 (38%) had a negative test result in their urethral or urine specimen. Among 163 patients who had only a rectal and/or pharyngeal specimen tested for GC, 16 (9.8%) were positive. If the clinic had tested only urethral or urine specimens, 33% of total gonorrhea cases among MSM [385 (369 + 16) of 1157] would have been missed.
Conclusion: GC screening strategies for MSM should include testing of rectal and pharyngeal specimens based on exposure. Given the decline of culture availability, efforts are needed to encourage laboratories to validate NAATs for rectal/pharyngeal specimens, which will likely increase exposure-based screening of MSM.
THE CENTERS FOR DISEASE CONTROL and Prevention (CDC) Sexually Transmitted Disease Treatment Guidelines recommend that men who have sex with men (MSM) be screened annually for gonorrhea (GC) infection at the urethral, rectal, and pharyngeal sites, based on exposure history1,2 with more frequent screening (3–6 months) recommended for MSM at the highest risk for STD transmission (e.g., having multiple partners or using illicit drugs). From a public health perspective, screening and treatment of GC is important to interrupt GC transmission and to help prevent the sexual transmission of HIV. Considerable epidemiologic data exist showing that GC and other STDs facilitate HIV transmission.3,4 From a biomedical perspective, it has been shown that among HIV-infected males, GC urethritis increases HIV concentration in semen 5- to 8-fold compared with HIV-infected men without urethritis.5,6 It is likely that the same inflammatory mechanism that occurs in urethritis also occurs in rectal GC infections. This supposition is supported by preliminary data from San Francisco, which suggests that 10% of HIV transmission in San Francisco is attributable to increased susceptibility or transmissibility caused by rectal GC or chlamydia (CT) infection.7
From 1975 through 1997, national gonorrhea (GC) reported incidence declined almost 75%, followed by a stable incidence for several years with a slight increase in 2005.8 In San Diego county, a similar pattern was evident with GC incidence declining through 1997. However, from 1997–2006, reported incidence of GC increased 84%, the male-to-female ratio increased from 1.2 to 1.3, and the reported number of rectal/pharyngeal GC infections among males increased more than 10-fold. In addition, a random sample survey of providers in San Diego who reported GC in 2001 showed that, at minimum, an estimated 23% of all reported GC in that year was accounted for by MSM.9 These data suggest that some of the increase in GC incidence in San Diego is occurring among MSM.
Considering the increase in GC among MSM and in light of the CDC GC screening recommendations for MSM, it is important to know the yield of different screening strategies. There are a variety of ways to diagnose GC at the urethral site—a urethral swab for Gram stain, GC culture, DNA probe, or nucleic acid amplification test (NAAT), or a urine NAAT. However, currently, the only FDA cleared test for GC at the rectal/pharyngeal site is GC culture. Because the introduction of FDA-approved urethral/urine nonculture GC tests, fewer GC cultures are being processed in public health laboratories10 and probably the same trend is occurring in commercial and other laboratories offering GC testing. It is likely that for MSM seeking care in a private practice setting, rectal/pharyngeal GC cultures are not being done and clinicians are relying solely on urethral/urine GC screening to detect GC infection. However, data are accumulating that show NAATs on specimens obtained from rectal or pharyngeal sites are sensitive and specific.11
Although some physicians caring for MSM probably realize that some GC infections will be missed using only urethral/urine specimens, there are little quantitative data available concerning this issue. To determine how often relying on a negative urethral/urine test alone in an STD Clinic setting will result in missing a GC infection at the rectal or pharyngeal site in an MSM, we examined data collected in the San Diego County STD Clinic during the period 1997–2003.
At the main public health STD clinic in San Diego county, male patients with urethral symptoms usually received a urethral smear for Gram stain to identify Gram-negative intracellular diplococci (presumptive GC) and a GC culture. For MSM without urethral symptoms, a urine NAAT for GC and chlamydia was usually done. MSM were asked about exposures and symptoms at the rectal/pharyngeal site within the past 3 months, and if reported, a site-specific GC culture was recommended. A case of GC among MSM was defined as any positive test (Gram stain, NAAT, or culture) from any of the 3 anatomical sites.
The results of all GC tests obtained from STD clinic patients were entered into the Public Health Laboratory computerized database. MSM were identified using the following criteria: (1) male-to-male sexual contact risk factor indicated on the laboratory test requisition, or (2) males without male-to-male sexual contact indicated, but a rectal culture was done (probable MSM). Males with no risk factor identified with only a pharyngeal culture were not included as MSM because heterosexual males having oral exposure to a female partner could have this test done (a random sample of patients’ medical charts showed that >95% of males with only pharyngeal culture were heterosexual, data not shown). Each reported test episode included in the analysis was from different sexual exposures (date of specimen collection >30 days apart) and urethral/urine tests were classified as 1 urethral site specimen. Some patients (<5%) had multiple episodes of GC during the 7-year study period and were included in the data each time.
Swab specimens for GC culture were directly streaked onto selective media, incubated in a carbon dioxide candle jar in the clinic, and transported daily to the Public Health Laboratory for additional incubation and culture identification. GC was identified through established culture routine. In addition, NAATs, using a ligase chain reaction (LCR) (Abbott LCx; Abbott Laboratories, Abbott Park, IL), were available from 1997 through 2001, and thereafter, a transcription-mediated amplification (TMA) (Gen-Probe APTIMA, Gen-Probe, San Diego, CA) chlamydia and gonorrhea combined NAAT was used for urethral/urine screening for the remaining years of the evaluation.
Because rectal/pharyngeal sexual exposure is the primary pathway to acquiring rectal/pharyngeal infection, it was assumed that MSM not reporting those exposures did not have rectal/pharyngeal infection. To obtain information about sites exposed, 2 random samples of MSM patients’ clinic charts were reviewed. Both samples were selected from MSM who had a negative urethral/urine test because patients in this group would not be identified as GC infected, unless the rectal/pharyngeal site had been tested and infections identified. In the first sample (N = 60), MSM with a GC positive rectal/pharyngeal test provided an estimate of the proportion of MSM with rectal/pharyngeal GC who reported exposure at the rectal/pharyngeal site (assumed to very high). In the second sample (N = 60), MSM with no test done at the rectal/pharyngeal site, provided an estimate of the proportion of MSM who had rectal/pharyngeal exposure (and possibly GC infection), but were not tested at those sites.
During the 7-year period, 7333 MSM were tested for GC. Of those, 94% were MSM as indicated by risk factor and the remaining 6% were probable MSM due to having a rectal culture done. Of the 7333 MSM tested, 1157 (15.8%) had a GC positive result at 1 or more sites. Overall positivity was higher among those <30 years of age compared with older patients [18.5% vs. 14.2%, prevalence ratio (PR) = 1.3, 95% confidence interval (CI) = 1.2–1.5, P <0.001]. Positivity was also higher among blacks compared with others (19.4%, vs. 15.5%, PR = 1.3, 95% CI = 1.1–1.5, P <0.05). Among 3158 MSM with other risk factor information, those reporting ≥3 sex partners in the past 3 months were more likely to have GC than those patients not reporting this risk factor (19.9% vs. 11.7%, PR = 1.7, 95% CI = 1.2–2.4, P <0.01).
The distribution of positivity rates by specimen sites are shown in Table 1. Of the 7333 MSM tested, 19% were tested at urethral site only, 2% at rectal or pharyngeal sites only, 35% at urethral plus rectal or pharyngeal sites, and 44% at all 3 sites. Overall, 10.8% of urethral/urine tests, 9.8% of rectal tests, and 4.0% of pharyngeal tests were positive. Among MSM patients with a negative urethral/urine test and a positive rectal/pharyngeal test (first sample of charts), as expected, 98% reported having had exposure at the rectal/pharyngeal site (pharyngeal 97%, rectal 93%, overall 98%). Less than half (38%) had symptoms. Presumptive treatment (before the GC positive result was known) had been given to 48%. Among the MSM patients with a negative urethral test and no rectal/pharyngeal test done (second sample of charts), 25% reported rectal/pharyngeal exposure during the past 3 months.
The STD Clinic would have missed a considerable number of GC infections if rectal/pharyngeal testing had not been done among MSM who reported rectal/pharyngeal exposure or symptoms. Among patients with a urethral test plus a rectal or pharyngeal test (N = 960), 369 (38%) were urethral test negative and rectal/pharyngeal tests positive (Table 2). In addition, among 163 other patients who had only rectal/pharyngeal tests, 16 were positive (Table 1). If the clinic had done only urethral testing of MSM patients, 33% of total GC infections among them [385 (369 + 16) of 1157] would have been missed.
This evaluation showed that 33% of the GC infections identified among MSM STD clinic patients would have been missed, if rectal/pharyngeal testing had not been done. These findings reaffirm those found more than 25 years ago that similarly showed that among MSM attending STD clinics, >35% of GC would have been missed (36%12, 42%13). Recently, in a 2003 study in the San Francisco City STD Clinic and the Gay Men’s Community Health Center, 56% of GC (502 of 892 total GC infections) would have been missed, if only urethral screening had been done.14 In a 2005 study done at a genitourinary medical clinic in London, UK, 18% of GC infections would have been missed.15 In the San Diego STD Clinic, the missed proportion (33%) was lower than that from San Francisco probably because of the lower pharyngeal infection rate in San Diego (4.0% in San Diego vs. 9.2% in San Francisco), which may be attributed to the fact that San Francisco used NAATs, which are more sensitive than culture, for testing rectal, and pharyngeal specimens. Regardless, these evaluations show that a considerable number of GC infections among MSM will be missed and many will likely be untreated, if screening and treatment are based only on urethral screening.
This evaluation also suggests that even using a protocol for testing all exposed sites, it is still likely that some infections will be missed and untreated. The first chart sample showed that essentially all positive rectal/pharyngeal tests were obtained from persons reporting exposures at those sites, which suggests that positivity among patients not reporting those exposures would be low. However, a period of universal screening would be needed to confirm this supposition. The second chart sample showed that 25% of persons with negative urethral tests reported exposure at those sites, but were not tested, which suggests some infections were missed (possibly as high as 9.8% would be positive based on the overall rectal tests positivity rate). Data about the reasons for not testing were not abstracted from the sample charts; it is likely that some patients declined testing.
This evaluation has several limitations. First, the number of MSM identified is very likely an underestimate because some MSM may not have disclosed that information, or it was not recorded in the laboratory requisition. Second, estimates obtained from the chart sampling of MSM with a negative urethral GC were based on a small sample size. Third, the exposure estimates among the sample of MSM with no rectal/pharyngeal tests done were not anatomical site-specific, but were recorded as a composite of rectal or pharyngeal exposures. Fourth, because GC culture of rectal and pharyngeal specimens is only about 60% to 75% sensitive, the proportion of GC infections missed reported in this evaluation is very likely an underestimate. Additional evaluations that collect site-specific exposure and rectal site test acceptance for all MSM clients, combined with a period of universal screening using NAATs, would determine the number of infections missed using the current exposure and symptom-based screening recommendations compared with offering 3-site testing to all MSM patients.
The findings from this STD Clinic evaluation estimate of missed infections using only urethral testing can be projected to what is very likely occurring among private providers who care for high-risk MSM patients. Little data are available regarding 3-site testing in the private sector. However, the random sample survey done among San Diego providers (N = 224) who reported GC in 2001, identified 16 patients with a positive rectal/pharyngeal test, and all but 1 were reported from the STD Clinic,9 suggesting that private providers are not testing at these anatomical sites and are relying on urethral testing only. However, though unlikely, private providers may be doing 3-site testing, but the positivity rate is much lower than that found in the STD Clinic. Alternatively, private providers may realize the potential for missing infections by not testing rectal/pharyngeal sites and may be presumptively treating high-risk MSM for GC, even if urethral testing is negative. Additional data are needed to answer these questions.
Since the introduction of NAATs for GC using urine specimens, the use of GC culture has been declining, and it is likely that more MSM with urethral negative-rectal/pharyngeal GC infection are being missed and untreated. Recent data have shown that NAATs for both GC and chlamydia at the rectal/pharyngeal site are sensitive and specific.11 Although these tests are not FDA cleared for use at these sites, laboratories can use NAATs for rectal/pharyngeal specimens, as long as they carry out a relatively simple validation procedure showing that the performance of these tests meets CLIA standards.16 Public Health Laboratories in San Francisco and San Diego have validated NAATs for rectal/pharyngeal sites and are identifying additional infections that would have been missed (unpublished data). Providers caring for MSM should encourage laboratories providing service for their patients to carry out the validation procedure and begin offering NAATs for specimens obtained from rectal and pharyngeal sites.
1. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep 2002; 51(RR-6):1–78.
2. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. MMWR Recomm Rep 2006; 55(RR-11):1–94.
3. Centers for Disease Control and Prevention. HIV prevention through early detection and treatment of sexually transmitted diseases. MMWR Recomm Rep 1998; 47(RR-12):1–24.
4. Cohen MS. Sexually transmitted diseases enhance transmission: No longer a hypothesis. Lancet 1998; 351(suppl 111):5–7.
5. Sadiq ST, Taylor S, Copas AJ, et al. The effects of urethritis on seminal plasma HIV-1 RNA loads in homosexual men not receiving antiretroviral therapy. Sex Transm Infect 2005; 81:120–123.
6. Cohen MS, Hoffman IF, Royce RA, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: Implications for prevention of sexual transmission of HIV-1. Lancet 1997; 349:1868–1873.
7. Kent CK, Ahrens K, Courtney JG, et al. Rectal chlamydia and gonococcal infections are common and have a substantial impact on HIV incidence among men who have sex with men in San Francisco. In: 1st International Workshop on HIV transmission, Principle of Intervention, August 12–14, 2006, Toronto, Canada. Abstract 23.
8. Center for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2005. Atlanta, GA: US Department of Health and Human Services, 2006:15.
9. Mark KE, Gunn RA. Gonorrhea surveillance: Estimating epidemiologic and clinical characteristics of reported cases using a sample survey methodology. Sex Transm Dis 2004; 31:215–220.
10. Dicker LW, Mosure DJ, Steece R, et al. Testing for sexually transmitted diseases in U.S. Public health laboratories in 2004. Sex Transm Dis 2007; 34:41–46.
12. Handsfield HH, Knapp JS, Diehr PK, et al. Correlation of auxotype and penicillin susceptibility of Neisseria gonorrhoeae
with sexual preference and clinical manifestations of gonorrhea. Sex Transm Dis 1980; 7:1–5.
13. Janda WM, Bohnhoff M, Morello JA, et al. Prevalence and site-pathogen studies of Neisseria meningitidis
and N gonorrhoeae
in homosexual men. JAMA 1980; 244:2060–2064.
14. Kent CK, Chaw JK, Wong G, et al. 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.
15. Benn PD, Rooney G, Carder C, et al. Chlamydia trachomatis and Neisseria gonorrhea
infection and the sexual behavior of men who have sex with men. Sex Transm Infect 2007; 83:106–12.
16. Renault CA, Hall C, Kent CK, et al. Use of NAATs for STD diagnosis of GC and CT in non-FDA-cleared anatomic specimens. Available at: www.PLO-online.com
. Accessed July 10–22, 2006.
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