Sexually Transmitted Diseases:
Mycoplasma genitalium Infection in Women Attending a Sexually Transmitted Infection Clinic: Diagnostic Specimen Type, Coinfections, and Predictors
Mobley, Victoria L. MD, MPH*; Hobbs, Marcia M. PhD*; Lau, Karen FNP*; Weinbaum, Barbara S. MS†; Getman, Damon K. PhD†; Seña, Arlene C. MD, MPH*
From the *Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC; and †Research and Development, Gen-Probe Inc., San Diego, CA
Supported by the National Institutes of Health/National Institute for Allergy and Infectious Disease grant 5 2 T32 AI 007001-34: Training in Sexually Transmitted Diseases and HIV and CTSA grant UL1RR025747 (to V.M.) and the Southeastern Sexually Transmitted Infections Cooperative Research Center grant U19-AI031496 (to M.M.H.).
Correspondence: Victoria L. Mobley, MD, MPH, Division of Infectious Diseases, University of North Carolina, Campus Box 7030, Chapel Hill, NC 25799. E-mail: email@example.com.
Received for publication May 3, 2010, and accepted January 20, 2012.
Abstract: In female sexually transmitted infection clinic attendees, Mycoplasma genitalium was more frequently detected using vaginal (53/73) versus endocervical (43/73) specimens. In women without other sexually transmitted infections, M. genitalium detection (N = 44) was associated with age ≤22 years (odds ratio, 2.53; P = 0.006) and clinical evidence of cervicitis (odds ratio, 2.11; P = 0.03).
Mycoplasma genitalium (MG) is an emerging sexually transmitted infection (STI) in women1–3 and has been associated with cervicitis,4–6 pelvic inflammatory disease2,6,7, and salpingitis.8,9 In high-risk women attending STI clinics, the MG prevalence is between 7% and 26%.10 Nucleic acid amplification tests (NAATs) have allowed MG detection for research purposes; however, the optimal genital specimen in women remains unclear. Some analyses reported the highest sensitivity for MG detection using vaginal specimens,11,12 whereas others observed a better performance with urine polymerase chain reaction (PCR) assays.13 Identification of the optimal specimen for MG detection in women is critical to facilitating its application in clinical practice.
MG has frequently been detected in women coinfected with other STIs, especially Chlamydia trachomatis (CT).14–16 In the absence of commercially available tests for MG detection, determining the likelihood of MG coinfections in women is particularly important in the clinical management of women with evidence of persistent urogenital tract infection despite treatment for other STIs. Assessing predictors of MG infection in the absence of other STIs is also essential to unraveling the independent role of this emerging infection.
We conducted a prospective cross-sectional study of women attending an STI clinic to (1) compare the MG detection rate of vaginal and endocervical swab specimens using NAATs, (2) determine the prevalence of MG coinfection among Neisseria gonorrhoeae (NG)-, CT-, and Trichomonas vaginalis (TV)-infected women, and (3) identify predictors of MG infection in the absence of other STIs.
English-speaking women, age ≥18 years, were recruited from a public STI clinic in Durham, NC between March 2007 and September 2008. All subjects provided written informed consent, and the study was approved by the Biomedical Institutional Review Board of the University of North Carolina. Each participant underwent a structured history and completed a questionnaire regarding demographic and behavioral risk factors. Vaginal swabs were collected for (1) routine wet mount microscopy, (2) InPouch TV culture (BioMed Diagnostics), and (3) transcription-mediated amplification (TMA) testing for TV using the APTIMA TV analyte-specific reagents (TV ASR)17 and a research TMA assay for MG (Gen-Probe, Inc.).15 Endocervical swabs were obtained for (1) Gram stain and (2) CT, NG, TV, and MG TMA testing. The Food and Drug Administration-cleared APTIMA Combo2 test was used for NG and CT detection according to the manufacturer's instructions (Gen-Probe, Inc.).
Cervicitis was defined clinically as the presence of purulent, mucopurulent, or yellow endocervical discharge or endocervical friability on speculum examination. MG-positive women who were negative for NG, CT, and TV infections were defined as being infected with MG-only. Women were considered asymptomatic if they reported the absence of vaginal discharge, vaginal irritation, dysuria, genital itching, lower abdominal pain, genital ulcers, or rashes. Vaginal discharge was clinically defined as the presence of any nonclear discharge on speculum examination. Bacterial vaginosis was diagnosed clinically using Amsel's criteria.18
Using an infected-patient standard (IPS), we defined MG positivity as a positive vaginal and/or endocervical TMA assay. The detection rate of vaginal and endocervical specimens was determined relative to the IPS-positive patients, and Cohen's kappa statistic (κ) was used to evaluate the agreement between the 2 specimens for MG detection.
The MG, NG, CT, and TV prevalence was determined using the number of positive results among all women tested for that pathogen. The prevalence of MG coinfections was calculated using the number detected with MG among women already identified with NG, CT, or TV infections. Pearson χ2 test was used to assess for associations between MG-only detection and patient demographic and clinical variables compared with that in women without detected STIs. Variables associated with MG-only at a P < 0.1 in bivariable analysis were included in multivariable logistic regression models to calculate adjusted odds ratios (OR) with 95% confidence intervals (CI). Statistical analyses were performed with Stata/IC version 11 (Stata Corp, College Station, TX).
We enrolled 381 women in this study, of which 89% were of black race/ethnicity; the median age was 26 (interquartile range: 21–35). Eighty percent of women reported at least 1 symptom, with vaginal discharge being the most common (54%).
Overall, the prevalence of MG was 19.2% (73/381) compared with 26.5% for TV, 12.6% for CT, and 6.0% for NG. MG coinfections were detected in 30.4% of women with NG, 25.0% with CT, and 19.8% with TV infections. Among women without other STIs, the prevalence of MG was 11.5% (44/381).
Of the 73 IPS-positive women, 53 (72.6%) were detected by vaginal specimens and 43 (58.9%) by endocervical specimens (Table 1). MG was detected by both genital specimens in 23/73 (32%) women, resulting in low-to-moderate agreement between the specimens (κ = 0.41). In comparison, good agreement (κ = 0.92) was observed between vaginal and endocervical specimens for TV detection, suggesting that the low agreement between specimens for MG detection was not attributable to collection techniques.
In bivariable analyses comparing women with MG-only to those without detectable STIs, MG was positively associated with age ≤22 years (P = 0.001), being asymptomatic (P = 0.02), and cervicitis (P = 0.03) and negatively associated with reported vaginal discharge (P = 0.03) and douching (P = 0.02) (Table 2). In multivariable analysis, age ≤22 years (OR, 2.53; 95% CI, 1.25–5.12) and cervicitis (OR, 2.11; 95% CI, 1.04–4.26) remained associated with MG-only detection. In multivariable analyses of each specimen type, age ≤22 years was associated with endocervical (N = 12; OR, 6.91; 95% CI, 1.65–28.9), but not vaginal (N = 20; OR, 2.16; 95% CI, 0.79–5.93), detection of MG-only. A trend was observed for an association between cervicitis and MG-only detection by endocervical (OR, 2.56; 95% CI, 0.67–9.76) and vaginal specimens (OR, 1.93; 95% CI, 0.72–5.20), although the estimates were imprecise given the small numbers of patients in each group.
In our study population, MG was detected more frequently than both NG and CT and was commonly isolated in women with other STIs. A higher prevalence of MG relative to CT has been observed by other investigators,6,15,16 and lower estimates reported in other studies may reflect regional differences in MG prevalence.
The vaginal swab specimen had a higher detection rate for MG than the endocervical swab specimen. Although we were limited by not having an independent comparator assay with which to determine the sensitivity of the genital specimens, our MG TMA research assay is likely to be more sensitive than DNA-based PCR methods, as it targets rRNA that is present in the cell in multiple copies as opposed to single-copy genes.12 The higher detection rate observed using vaginal versus endocervical specimens supports the findings of other investigators.11,12,16 This may reflect minimal host immune response to MG infection in the vaginal epithelium, and thus greater bacterial survival in the vagina compared with the endocervix, where the inflammatory response to MG by endocervical epithelial cells is more robust.19 This may also explain reported associations between MG and cervicitis,3–5 but not vaginitis.20
Although more cases of MG were detected using vaginal specimens, more than one-quarter of MG-positive women would have been missed using either specimen type alone. Lillis et al reported relative sensitivities for vaginal and endocervical specimens of 85.7% and 74.3%, respectively using a PCR assay, which increased to >95% when the results of the 2 specimens were combined.11 However, testing from multiple specimens is not feasible in resource-limited settings such as public STI clinics. Self-collected vaginal swabs are preferred by women and have higher sensitivities for STI detection than more invasive forms of specimen collection.12,21–23 Therefore, the testing of a single self-collected vaginal swab for NG, CT, TV, and MG may result in the most cost-effective screening recommendation; however, the performance of self-collected vaginal specimens for MG detection remains to be determined.
In MG-positive women without other coinfections, young age and cervicitis were the only patient characteristics associated with MG detection. Being asymptomatic was associated with a 2-fold increased risk of detecting MG-only, but was only significant in bivariable analyses; this finding, which has been noted by others,24 suggests that MG infections in women may not be associated with specific urogenital symptoms. The association between young age and MG detection has been previously observed25–27 and is likely mediated by both biologic (i.e., endocervical ectopy) and behavioral (i.e., number of sexual partners and inconsistent condom use) risk factors.28,29 The association between MG and cervicitis has been reported by some investigators,3–6 but not others,14,15,30 which likely stems from the wide discrepancy in how cervicitis is defined.
In conclusion, NAATs using vaginal specimens for MG detection provide higher detection rates than endocervical specimens, but would still miss a fourth of infections that we identified using an IPS. Women with CT, NG, and TV infections have a high prevalence of MG coinfection; however, MG prevalence is also high at 11.5% among women without other STIs. Young age and cervicitis were the only predictors significantly associated with MG-only infection in our study, and we found no associations with urogenital symptoms. Therefore, if NAATs for MG detection become commercially available, clinicians should consider screening young asymptomatic women with cervicitis but recognize the potential limitations of the assay.
1. Manhart LE. Has the time come to systematically test for Mycoplasma genitalium? Sex Transm Dis 2009; 36:607–608.
2. Haggerty CL, Totten PA, Astete SG, et al.. Mycoplasma genitalium among women with nongonococcal, nonchlamydial pelvic inflammatory disease. Infect Dis Obstet Gynecol 2006; 2006:30184.
3. Anagrius C, Loré B, Jensen JS. Mycoplasma genitalium: Prevalence, clinical significance, and transmission. Sex Transm Infect 2005; 81:458–462.
4. Falk L, Fredlund H, Jensen JS. Signs and symptoms of urethritis and cervicitis among women with or without Mycoplasma genitalium or Chlamydia trachomatis infection. Sex Transm Infect 2005; 81:73–8.
5. Manhart LE, Critchlow CW, Holmes KK, et al.. Mucopurulent cervicitis and Mycoplasma genitalium. J Infect Dis 2003; 187:650–657.
6. Gaydos C, Maldeis NE, Hardick A, et al.. Mycoplasma genitalium as a contributor to the multiple etiologies of cervicitis in women attending sexually transmitted disease clinics. Sex Transm Dis 2009; 36:598–606.
7. Cohen CR, Manhart LE, Bukusi EA, et al.. Association between Mycoplasma genitalium and acute endometritis. Lancet 2002; 359:765–766.
8. Ross JD, Jensen JS. Mycoplasma genitalium as a sexually transmitted infection: Implications for screening, testing, and treatment. Sex Transm Infect 2006; 82:269–271.
9. Clausen HF, Fedder J, Drasbek M, et al.. Serological investigation of Mycoplasma genitalium in infertile women. Hum Reprod 2001; 16:1866–1874.
10. Manhart LE, Kay N.. Mycoplasma genitalium: Is it a sexually transmitted pathogen? Curr Infect Dis Rep 2010; 12:306–313.
11. Lillis RA, Nsuami MJ, Myers L, et al.. Utility of urine, vaginal, cervical, and rectal specimens for detection of Mycoplasma genitalium in women. J Clin Microbiol 2011; 49:1990–1992.
12. Wroblewski JK, Manhart LE, Dickey KA, et al.. Comparison of transcription-mediated amplification and PCR assay results for various genital specimen types for detection of Mycoplasma genitalium. J Clin Microbiol 2006; 44:3306–3312.
13. Jensen JS, Björnelius E, Dohn B, et al.. Comparison of first void urine and urogenital swab specimens for detection of Mycoplasma genitalium and Chlamydia trachomatis by polymerase chain reaction in patients attending a sexually transmitted disease clinic. Sex Transm Dis 2004; 31:499–507.
14. Tosh AK, Van Der Pol B, Fortenberry JD, et al.. Mycoplasma genitalium among adolescent women and their partners. J Adolesc Health 2007; 40:412–417.
15. Huppert JS, Mortensen JE, Reed JL, et al.. Mycoplasma genitalium detected by transcription-mediated amplification is associated with Chlamydia trachomatis in adolescent women. Sex Transm Dis 2008; 35:250–254.
16. Casin I, Vexiau-Robert D, De La Salmonière P, et al.. High prevalence of Mycoplasma genitalium in the lower genitourinary tract of women attending a sexually transmitted disease clinic in Paris, France. Sex Transm Dis 2002; 29:353–359.
17. Huppert JS, Mortensen JE, Reed JL, et al.. Rapid antigen testing compares favorably with transcription-mediated amplification assay for the detection of Trichomonas vaginalis in young women. Clin Infect Dis 2007; 45:194–198.
18. Amsel R, Totten PA, Spiegel CA, et al.. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983; 74:14–22.
19. McGowin CL, Popov VL, Pyles RB. Intracellular Mycoplasma genitalium infection of human vaginal and cervical epithelial cells elicits distinct patterns of inflammatory cytokine secretion and provides a possible survival niche against macrophage-mediated killing. BMC Microbiol 2009; 9:139.
21. Shafer MA, Moncada J, Boyer CB, et al.. Comparing first-void urine specimens, self-collected vaginal swabs, and endocervical specimens to detect Chlamydia trachomatis and Neisseria gonorrhoeae by a nucleic acid amplification test. J Clin Microbiol 2003; 41:4395–4399.
22. Richardson E, Sellors JW, Mackinnon S, et al.. Prevalence of Chlamydia trachomatis infections and specimen collection preference among women, using self-collected vaginal swabs in community settings. Sex Transm Dis 2003; 30:880–885.
23. Masek BJ, Arora N, Quinn N, et al.. Performance of three nucleic acid amplification tests for detection of Chlamydia trachomatis and Neisseria gonorrhoeae by use of self-collected vaginal swabs obtained via an Internet-based screening program. J Clin Microbiol 2009; 47:1663–1667.
24. Andersen B, Sokolowski I, Østergaard L, et al.. Mycoplasma genitalium: Prevalence and behavioural risk factors in the general population. Sex Transm Infect 2007; 83:237–241.
25. Hancock EB, Manhart LE, Nelson SJ, et al.. Comprehensive assessment of sociodemographic and behavioral risk factors for Mycoplasma genitalium infection in women. Sex Transm Dis 2010; 7:777–783.
26. Oakeshott P, Hay P, Taylor-Robinson D, et al.. Prevalence of Mycoplasma genitalium in early pregnancy nd relationship between its presence and pregnancy outcome. BJOG 2004; 111:1464–1467.
27. Short VL, Totten PA, Ness RB, et al.. The demographic, sexual health and behavioural correlates of Mycoplasma genitalium infection among women with clinically suspected pelvic inflammatory disease. Sex Transm Infect 2010; 86:29–31.
28. Niccolai LM, Ethier KA, Kershaw TS, et al.. New sex partner acquisition and sexually transmitted disease risk among adolescent females. J Adolesc Health 2004; 34:216–223.
29. Critchlow CW, Wölner-Hanssen P, Eschenbach DA, et al.. Determinants of cervical ectopia and of cervicitis: age, oral contraception, specific cervical infection, smoking, and douching. Am J Obstet Gynecol 1995; 173:534–543.
30. Korte JE, Baseman JB, Cagle MP, et al.. Cervicitis and genitourinary symptoms in women culture positive for Mycoplasma genitalium. Am J Reprod Immunol 2006; 55:265–275.
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