Guidelines recommend screening men who have sex with men (MSM) for rectal and pharyngeal gonorrhea,1,2 which are mostly asymptomatic,3,4 whereas urethral gonorrhea usually presents with symptoms of urethritis.3,5 Previously, culture was the laboratory method of choice for gonorrhea testing, but this has been superseded by nucleic acid amplification testing (NAAT), which has been shown to be more sensitive for detection of gonorrhea at the rectum6–8 and pharynx.8,9
This before-and-after study aimed to measure the impact of a change in testing methods from culture to NAAT on the detection of rectal and pharyngeal gonorrhea in MSM on a sexual health service level. We also examined the effect of this change on the detection of gonorrhea in subgroups of men where higher rates of gonorrhea are anticipated.
This study was conducted at the Melbourne Sexual Health Centre. Men who have sex with men attending the clinic for sexually transmitted infection screening were screened according to Australian guidelines,10 which included pharyngeal and anal swabs for gonorrhea. Tests for urethral gonorrhea were performed only in men with symptomatic urethritis. We included data from clinic visits for all men who reported sex with men, and who had been tested for gonorrhea at the rectum and/or pharynx. To exclude tests of cure, we excluded visits from men who tested for gonorrhea within 30 days of a previous gonorrhea test.
Before March 2015, all testings for gonorrhea comprised culture of clinician-collected anal and pharyngeal swabs, as described elsewhere.11 In late March 2015, laboratory testing changed from culture to NAAT using the Aptima Combo 2 (AC2) assay for screening, and the Aptima GC test for confirmation of all positive samples, on the Hologic Panther Platform.12 Culture testing continued for a month (April 2015) after the introduction of NAAT.
We compared detection of rectal and pharyngeal gonorrhea between 2 periods: the “culture period” (April to December 2014) and the “NAAT period” (April to December 2015). Subgroup analyses were conducted for MSM reporting recent sexual contact with gonorrhea, and MSM who presented with symptomatic proctitis, as defined elsewhere.13,14 We compared gonorrhea positivity between HIV-positive and HIV-negative MSM. We also compared NAAT and culture detection in men tested using both methods during the month of dual testing.
Statistical analyses were conducted using STATA (version 13.1). 95% confidence intervals (CI) for gonorrhea test positivity were calculated using the “exact” binomial distribution. Prevalence ratios (PR) were calculated using generalized linear models with log-link and binomial distribution. Data for the month of dual culture and NAAT testing within individuals were treated as paired data and analyzed using McNemar's tests.
We assessed whether underlying population prevalence of gonorrhea may have differed in the 2 periods by comparing patient sexual risk behavior and by determining the positivity of urethral gonorrhea by culture as a proxy for gonorrhea incidence. Each period covered similar seasons to control for potential seasonal differences in gonorrhea rates.15
Ethical approval was obtained from the Alfred Hospital Research Ethics Committee (424/15).
Men who have sex with men in the culture period were similar to MSM in the NAAT period with regard to age, HIV status, and number of sexual partners (Table 1). Slightly more men reported consistent use of condoms for receptive and/or insertive anal sex in the culture period compared with the NAAT period (50.3% vs 52.8%, P = 0.011).
Among all MSM tested for extragenital gonorrhea, 3.9% of anal swabs were positive for gonorrhea during the culture period, and 8.0% during the NAAT period (PR, 2.0; 95% CI, 1.8–2.4) (Table 1). 1.6% of pharyngeal swabs were positive for gonorrhea during the culture period, and 8.3% during the NAAT period (PR, 5.2; 95% CI, 4.2–6.4) (Table 1).
Among HIV-positive men, the positivity of rectal gonorrhea increased from 9.6% to 15.4% (PR, 1.6; 95% CI, 1.2–2.2); and the positivity of pharyngeal gonorrhea increased from 1.5% to 9.9% (PR, 6.8; 95% CI, 3.4–13.5). Among HIV-negative men, the positivity of rectal gonorrhea increased from 3.3% to 7.3% (PR, 2.2; 95% CI, 1.9–2.6), and the positivity of pharyngeal gonorrhea increased from 1.6% to 8.1% (PR, 5.0; 95% CI, 4.0–6.2) (Table 1). Using NAAT, test positivity for gonorrhea at the pharynx was similar for HIV-positive and HIV-negative men (9.9% vs 8.1%; PR, 1.21; 95% CI, 0.95–1.55), but positivity at the rectum was double in HIV-positive compared with HIV-negative men (15.4% vs 7.3%; PR, 2.1; 95% CI, 1.7–2.6).
Among men who reported contact with another man with gonorrhea, there was no difference in test positivity for rectal gonorrhea by culture (24.9%) compared with NAAT (25.3%). By contrast, test positivity for pharyngeal gonorrhea was 3 times higher by NAAT (25.8%) compared with culture (8.7%) (PR, 3.0; 95% CI, 1.9–4.7). Among men with symptomatic proctitis, there was no significant difference in test positivity for rectal gonorrhea by culture or NAAT, at 22.2% and 27.9%, respectively (PR, 1.3; 95% CI, 0.8–2.0) (Table 1).
During the period of dual culture and NAAT testing, 702 MSM were tested for rectal gonorrhea using both methods. Of the 67 MSM positive for rectal gonorrhea by NAAT, 39 tested positive by culture, representing sensitivity of 58% for rectal gonorrhea (Table 2A). Seven hundred sixty-three MSM tested for pharyngeal gonorrhea using NAAT and culture. Of the 68 MSM positive for pharyngeal gonorrhea by NAAT, 18 tested positive by culture (Table 2B), representing sensitivity of 26% for pharyngeal gonorrhea, which was significantly lower than for rectal gonorrhea (P = 0.02).
This study demonstrated that a change from culture to NAAT resulted in a substantial increase in detection of rectal and pharyngeal gonorrhea, of 2-fold and 5-fold, respectively. Although commercially available, gonorrhea NAATs have not been validated for use at extragenital sites, our results support current guidelines that recommend NAAT for screening of rectal and pharyngeal gonorrhea.2,16 Culture remains important for surveillance for antimicrobial resistance.17
The higher sensitivity of NAAT in our study was particularly striking for the detection of pharyngeal gonococci. A previous study showed that gonococcal loads were higher for infections that were both NAAT-positive and culture-positive compared with NAAT-positive culture-negative infections, suggesting that culture may miss lower-load gonococcal infections.18 In the same study, gonococcal loads at the pharynx were significantly lower than those at the rectum.18 This might explain why we found such a striking increase in detection of pharyngeal gonorrhea after switching from culture to NAAT, particularly as the AC2 assay has superior sensitivity over other NAATs.6,7,9
A similar US study by Barbee et al19 found that gonorrhea detection increased by 8% for rectal infections and by 12% for pharyngeal infections after changing from culture to the AC2 test, this increase in gonorrhea detection is smaller than in our study. However, in Barbee's study diagnoses of urethral gonorrhea declined significantly between their period of culture testing (2010) and AC2 testing (2011), suggesting a decline in the population prevalence of gonorrhea. After adjusting for this decline, they found that NAAT increased detection of pharyngeal gonorrhea by 74% and rectal gonorrhea by 66%. Our study also found a decline in cases of urethral gonorrhea, but this was not statistically significant. Another possible explanation for the difference between Barbee's finding and ours is that a proportion of samples in their study were self-collected: 15% of pharyngeal swabs and 43% of rectal swabs, whereas specimens in our study were clinician-collected. Previous studies have shown that optimal detection of pharyngeal gonorrhea is dependent on the adequacy of sampling, and this applies whether using culture or NAAT.11,20,21 The importance of sampling technique for the optimal detection of pharyngeal gonorrhea was emphasized to clinicians at our clinic before the start of this evaluation.
The increase in detection of pharyngeal and rectal gonorrhea was similar for HIV-positive and HIV-negative men. However, HIV-positive men had double the NAAT positivity of rectal gonorrhea compared with HIV-negative men, with no difference in pharyngeal gonorrhea by NAAT. Higher rates of gonorrhea in HIV-positive compared with HIV-negative MSM have recently been reported in the United Kingdom22 and may reflect higher frequency of condomless receptive anal sex.23
Among men reporting contact with gonorrhea, NAAT increased detection of pharyngeal gonorrhea 3-fold, but detection of rectal gonorrhea was similar for culture and NAAT. We speculate that these men may have had high gonococcal loads in their rectum and thus relatively high positivity by culture. Hypothetically, MSM with high rectal gonococcal loads may be more likely to transmit infection to partners who then develop symptomatic urethritis, resulting in partner notification. Men with symptomatic proctitis had similar gonorrhea positivity by NAAT and culture. This finding fits with the finding that men with symptomatic proctitis have higher gonococcal loads,18 which may explain why culture performs relatively well in these men.
This was a before-and-after study; hence, our results may have been affected by changes in the underlying prevalence of gonorrhea during the comparison periods. Numbers of sexual partners were similar in the two periods, but condom use was slightly less consistent in the NAAT period. Cases of urethral gonorrhea were somewhat fewer during the NAAT period.
This study demonstrates the superior sensitivity of NAAT compared to culture for the detection of extragenital gonorrhea in MSM on a health service level, particularly for pharyngeal infections. The improvement in detection by NAAT was similar among HIV-positive and HIV-negative MSM.
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