Bacteriology
The use and performance of oral–throat rinses to detect pharyngeal Neisseria gonorrhoeae and Chlamydia trachomatis infections

https://doi.org/10.1016/j.diagmicrobio.2007.05.010Get rights and content

Abstract

Gonococcal and chlamydial infections in the pharynx can occur as a consequence of oral sex. Currently, diagnosis of these infections typically requires a swab specimen to be collected from the posterior pharynx. However, we assessed the diagnostic adequacy of using commercial mouthwash or water as an oral–throat rinse and subsequent testing with a nucleic acid amplification test (Gen-Probe APTIMA Combo 2 assay; Gen-Probe, San Diego, CA). Mouthwash and water samples, spiked with varying amounts of gonorrhea and chlamydia, remained positive for both organisms for up to 2 weeks after storage at room temperature and 37 °C. A clinical trial compared the test performance of oral–throat rinses to pharyngeal swabs among 561 (250 mouthwash, 311 water) gay and other men who have sex with men. Participants were also surveyed to assess the acceptability, preference, and feasibility of oral–throat rinses in a clinical setting. The prevalence of pharyngeal gonorrhea and chlamydia were 9.5% (53/556) and 1.4% (8/561), respectively. Compared with the pharyngeal swab, mouthwash oral–throat rinses had a sensitivity and specificity for the detection of gonorrhea of 72% and 99.1%, respectively, whereas water had 82% and 99.7%, respectively. Chlamydia prevalence was too low for reliable assessments of test performance. Study participants found oral–throat rinses acceptable, preferable, and feasible when compared with pharyngeal swabs. Further study is needed to investigate discordant results and improve the sensitivity of oral–throat rinses.

Introduction

Among gay and other men who have sex with men (MSM), a substantial number of Neisseria gonorrhoeae and Chlamydia trachomatis infections occur at nongenital anatomic sites (Lafferty et al., 1997, Page-Shafer et al., 2002, Sulaiman et al., 1981). Recognition and management of these infections are critical for sexually transmitted disease (STD) control and to improve the sexual health of gay and other MSM. The Centers for Disease Control and Prevention (CDC, 2006) recommends annual pharyngeal testing for gonorrhea in MSM who report performing oral sex in the preceding year. For MSM at higher risk (those who have multiple or anonymous sex partners, who have sex in conjunction with illicit drug use, who use methamphetamine, or whose sex partners participate in these activities), CDC recommends screening every 3 to 6 months.

Pharyngeal infection with gonorrhea or chlamydia is predominately asymptomatic (Bro-Jorgensen and Jensen, 1973, Jebakumar et al., 1995, Lafferty et al., 1997, Page-Shafer et al., 2002). Although pharyngeal pathology is uncommon (Metzger, 1970, Wiesner et al., 1973), there is evidence that these infections, as well as those caused by other sexually transmitted organisms as well as nonsexually transmitted organisms (Bradsha et al., 2006), can be transmitted from the pharynx to the genital tract of sex partners (Bro-Jorgensen and Jensen, 1973, Edwards and Carne, 1998, Lafferty et al., 1997, Soendjojo, 1983, Tice and Rodriguez, 1981), thereby contributing to overall STD morbidity within a community. The lack of overt clinical signs for pharyngeal infection and the public health importance of identifying and treating infected individuals require adequate laboratory tools as an aid to the diagnosis.

Traditionally, culture has been used for the detection of pharyngeal infection with gonorrhea or chlamydia. However, nucleic acid amplification tests (NAATs) may be preferable to culture for pharyngeal infection detection owing to their increased test sensitivity (Page-Shafer et al, 2002) and availability in US public and private health laboratories (Dicker et al., 2007). Previous studies have shown increased detection of pharyngeal gonorrhea using ligase chain reaction (Page-Shafer et al., 2002, Stary et al., 1997, Young et al., 2003) and chlamydia using polymerase chain reaction (Jebakumar et al., 1995) on swab specimens. Because pharyngeal specimens have not been cleared by the Food and Drug Administration (FDA) to be tested by NAATs, laboratories must verify the procedure before reporting results to clinicians for patient management (Elder et al., 1997). Only a small number of laboratories, such as the San Francisco Department of Public Health Laboratory (SFDPHL) (Klausner et al., 2002), have verified the performance of NAATs against culture for nongenital infections caused by N. gonorrhoeae and C. trachomatis. There have been some concerns regarding the potential for some NAATs to cross-react with nongonococcal Neisseria spp. and other organisms commonly found in the throat, but the pattern of cross-reaction between tests is not uniform, and there have been no such reports of cross-reactivity when using the Gen-Probe APTIMA Combo 2® assay (Gen-Probe, San Diego, CA) (Whiley et al., 2006).

Because NAATs can detect organisms in urine specimens, they might also be able to detect gonorrhea and chlamydia in oral–throat rinse specimens. Although pharyngeal swab collection requires trained clinicians, oral–throat rinses can be collected by minimally trained staff or may even be amenable to self-collection at nonclinical settings such as in the home or field. Oral–throat rinses have been studied previously as a means to detect the presence of human papillomavirus, Candida dubliniensis, and Pneumocystis carinii (D'Souza et al., 2005, Helweg-Larsen et al., 1998, Lawton et al., 1992, Tekeli et al., 2005). Mouthwash might be an appropriate rinse agent because its high alcohol content (>15%) could help stabilize gonococcal and chlamydial nucleic acids. However, because commercial mouthwash formulation could change over time and vary by brand and type, changes in formulation or type would require additional verification studies. Thus, water might be a more practical long-term oral–throat rinse agent. The purposes of this study were A) to determine the analytic sensitivity of a nucleic acid amplification assay for N. gonorrhoeae and C. trachomatis; B) to compare the detection of N. gonorrhoeae and C. trachomatis from oral–throat rinses versus pharyngeal swabs collected from patients at risk for pharyngeal infection; and C) to assess the acceptability, preference, and feasibility of collecting oral–throat rinses versus pharyngeal swabs.

Section snippets

Analytic detection

A commercial mouthwash (green FreshBurst® Listerine® [21.6% alcohol] distributed by Pfizer, Morris Plains, NJ) and water were inoculated with N. gonorrhoeae or C. trachomatis at estimated concentrations of 10 to 107 colony forming units (CFUs) or inclusion forming units (IFUs) per milliliter, respectively. Specimens were tested for N. gonorrhoeae and C. trachomatis by the Gen-Probe APTIMA Combo 2 assay as described in the product insert after incubation at room temperature (25 °C) and 37 °C for

Analytic detection

All spiked specimens maintained at 25 °C were positive for N. gonorrhoeae- and C. trachomatis-specific RNA sequences, whereas uninoculated fluid remained negative (Fig. 1, Fig. 2). Relative light units (RLUs) declined but remained far above the negative cutoff for up to 14 days postinoculation. Similar results were observed with specimens incubated at 37 °C.

Clinical study

Forty-eight percent of eligible patients (566/1172) were enrolled into the study. A total of 556 subjects were tested for gonorrhea, and

Discussion

The increasing recognition of pharyngeal N. gonorrhoeae and C. trachomatis infections (Kent et al., 2005, Page-Shafer et al., 2002, Sulaiman et al., 1981) and their role in the continued spread of STDs have caused clinicians to request increasing diagnostic support from the clinical microbiology laboratory. Although NAATs for N. gonorrhoeae and C. trachomatis are not cleared by the FDA for pharyngeal specimens, their diagnostic utility has been proven (Jebakumar et al., 1995, Page-Shafer et

Acknowledgments

The authors would like to thank the San Francisco Department of Public Health (SFDPH) City Clinic staff and clinicians for their diligent work recruiting and enrolling patients into our study; Leah Rausch and Dr. Sally Liska from SFDPHL for performing additional tests on positive specimens; and Carol Farshy for performing in vitro experiments at the CDC. We also thank Gen-Probe for donating all the test kits and laboratory supplies. In addition, we thank the City Clinic patients who have

References (25)

  • D.M. Whiley et al.

    Nucleic acid amplification testing for Neisseria gonorrhoeae

    J. Mol. Diagn.

    (2006)
  • C. Bradsha et al.

    Etiologies of nongonococcal urethritis: bacteria, viruses, and the association with orogenital exposure

    J. Infect. Dis.

    (2006)
  • A. Bro-Jorgensen et al.

    Gonococcal pharyngeal infections. Report of 110 cases

    Br. J. Vener. Dis.

    (1973)
  • Centers for Disease Control and Prevention

    Sexually transmitted disease treatment guidelines, 2006

    MMWR Morb. Mortal. Wkly. Rep.

    (2006)
  • G. D'Souza et al.

    Analysis of the effect of DNA purification on detection of human papillomavirus on oral rinse samples by PCR

    J. Clin. Microbiol.

    (2005)
  • L.W. Dicker et al.

    Testing for sexually transmitted diseases in U.S. public health laboratories in 2004

    Sex. Transmit. Dis.

    (2007)
  • S. Edwards et al.

    Oral sex and the transmission of non-viral STIs

    Sex. Transm. Infect.

    (1998)
  • B.L. Elder et al.
  • J. Helweg-Larsen et al.

    Diagnostic use of PCR for detection of Pneumocystis carinii in oral wash samples

    J. Clin. Microbiol.

    (1998)
  • S.P.R. Jebakumar et al.

    Value of screening for oro-pharyngeal Chlamydia trachomatis infection

    J. Clin. Pathol.

    (1995)
  • C.K. Kent 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)
  • J.D. Klausner et al.

    Increased prevalence of Chlamydia trachomatis rectal infections with nucleic acid amplification testing: implications for screening

  • Cited by (24)

    • The JAID/JSC guidelines to Clinical Management of Infectious Disease 2017 concerning male urethritis and related disorders

      2021, Journal of Infection and Chemotherapy
      Citation Excerpt :

      Rare cases complain pharyngeal pain and hoarseness. Both N. gonorrhoeae and C. trachomatis can be detected by NAATs [29,30,32,34,35,37–40] (II, B). Some uncertain points, such as the timing of tests remain about NAATs to evaluate the effectiveness of antibiotics for pharyngeal infection.

    • Pharyngitis

      2014, Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
    • Transmission of Nonviral Sexually Transmitted Infections and Oral Sex

      2012, Journal of Sexual Medicine
      Citation Excerpt :

      None of these patients had any symptoms of pharyngitis. Diagnosis of pharyngeal C. trachomatis infection requires a posterior pharynx swab or mouthwash oral–throat rinses [50]. In particular, C. trachomatis has been isolated from the throat of a patient affected by TRIC ocular disease, likely secondary to infection or contamination of the throat by the nasolacrimal secretions [51].

    View all citing articles on Scopus
    View full text