In female sexually transmitted infection (STI) clinic attendees, Mycoplasma genitalium (MG) was more frequently detected using vaginal (53/73) versus endocervical (43/73) specimens. In women without other STIs, MG detection (N=44) was associated with age≤ 22 years (odds ratio (OR) 2.53, P=0.006) and clinical evidence of cervicitis (OR 2.11, P=0.03)

Getman, Damon K.

Hobbs, Marcia M.

Lau, Karen

Mobley, Victoria L.

Seña, Arlene C.

Weinbaum, Barbara S.

Carolina Digital Repository

Mycoplasma genitalium infection in women attending an STIclinic: diagnostic specimen type, co-infections, and predictorsVictoria L. Mobley, MD MPH1, Marcia M. Hobbs, PhD1, Karen Lau, FNP1, Barbara S.Weinbaum, MS2, Damon K. Getman, PhD2, and Arlene C. Seña, MD, MPH11University of North Carolina-Chapel Hill, NC2Research and Development, Gen-Probe Inc., San Diego, CAAbstractIn female sexually transmitted infection (STI) clinic attendees, Mycoplasma genitalium (MG) wasmore frequently detected using vaginal (53/73) versus endocervical (43/73) specimens. In womenwithout other STIs, MG detection (N=44) was associated with age≤ 22 years (odds ratio (OR)2.53, P=0.006) and clinical evidence of cervicitis (OR 2.11, P=0.03).KeywordsMycoplasma genitalium; detection rate; cervicitisMycoplasma genitalium (MG) is an emerging sexually transmitted infection (STI) inwomen,[1-3] and has been associated with cervicitis[4-6], pelvic inflammatory disease(PID)[2, 6, 7] and salpingitis.[8, 9] In high-risk women attending STI clinics, the MGprevalence is between 7-26%.[10] Nucleic acid amplification tests (NAATs) have allowedMG detection for research purposes; however, the optimal genital specimen in womenremains unclear. Some analyses reported the highest sensitivity for MG detection usingvaginal specimens, [11, 12] whereas others observed a better performance with urine PCR.[13]Identification of the optimal specimen for MG detection in women is critical to facilitatingits application in clinical practice.MG has frequently been detected in women co-infected with other STIs, especiallyChlamydia trachomatis (CT).[14-16] In the absence of commercially available tests for MGdetection, determining the likelihood of MG co-infections in women is particularlyimportant in the clinical management of women with evidence of persistent urogenital tractinfection despite treatment for other STIs. Assessing predictors of MG infection in theabsence of other STIs is also essential to unraveling the independent role of this emerginginfection.We conducted a prospective, cross-sectional study of women attending a STI clinic to: 1)compare the MG detection rate of vaginal and endocervical swab specimens using nucleicCorrespondence: Victoria Mobley, MD MPH, University of North Carolina at Chapel Hill, Division of Infectious Diseases, CampusBox 7030, Chapel Hill, NC 25799. victoria_mobley@med.unc.edu. Telephone (919) 843-3042, Fax (919) 966-6714..Conflict of Interest: NoneThis is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providingthis early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before itis published in its final citable form. Please note that during the production process errors may be discovered which could affect thecontent, and all legal disclaimers that apply to the journal pertain.NIH Public AccessAuthor ManuscriptSex Transm Dis. Author manuscript; available in PMC 2013 September 01.Published in final edited form as:Sex Transm Dis. 2012 September ; 39(9): 706–709. doi:10.1097/OLQ.0b013e318255de03.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptacid amplification tests (NAATs); 2) determine the prevalence of MG co-infection amongNG, CT and TV-infected women; 3) identify predictors of MG infection in the absence ofother STIs.English-speaking women, age ≥18 years, were recruited from a public STI clinic in Durham,North Carolina between March 2007 and September 2008. All subjects provided writteninformed consent and the study was approved by the Biomedical Institutional Review Boardof the University of North Carolina. Each participant underwent a structured history andcompleted a questionnaire regarding demographic and behavioral risk-factors. Vaginalswabs were collected for: 1) routine wet mount microscopy, 2) InPouch TV culture (BioMedDiagnostics) and 3) transcription-mediated amplification (TMA) testing for TV using theAPTIMA 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,Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and MG TMA testing. The FDA-cleared APTIMA Combo2 test was used for NG and CT detection according to themanufacturer’s instructions (Gen-Probe, Inc.).Cervicitis was defined clinically as the presence of purulent, mucopurulent or yellowendocervical discharge or endocervical friability on speculum exam. MG-positive womenwho 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 vaginaldischarge, vaginal irritation, dysuria, genital itching, lower abdominal pain, genital ulcers orrashes. Vaginal discharge was clinically defined as the presence of any non-clear dischargeon speculum exam. Bacterial vaginosis (BV) was diagnosed clinically using Amsel’sCriteria.[18]Using an infected-patient standard (IPS), we defined MG positivity as a positive vaginaland/or endocervical TMA assay. The detection rate of vaginal and endocervical specimenswere determined relative to the IPS-positive patients and Cohen’s kappa statistic (κ) wasused to evaluate the agreement between the two specimens for MG detection.The MG, NG, CT and TV prevalence was determined using the number of positive resultsamong all women tested for that pathogen. The prevalence of MG co-infections wascalculated using the number detected with MG among women already identified with NG,CT, or TV infections. Pearson’s chi-squared test was used to assess for associations betweenMG-only detection and patient demographic and clinical variables compared to that inwomen without detected STIs. Variables associated with MG-only at a P<0.1 in bivariableanalysis were included in multivariable logistic regression models to calculate adjusted oddsratios (OR) with 95% confidence intervals (CI). Statistical analyses were performed withStata/IC version 11 (Stata Corp, College Station, TX).We enrolled 381 women in this study, of which 89% were of black race/ethnicity; themedian age was 26 (interquartile range [IQR]: 21-35). Eighty percent of women reported atleast one symptom, with vaginal discharge being the most common (54%).Overall, the prevalence of MG was 19.2% (73/381), compared to 26.5% for TV, 12.6% forCT and 6.0% for NG. MG co-infections 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 prevalenceof 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 specimensin 23/73 (32%) women, resulting in low to moderate agreement between the specimens(κ=0.41). In comparison, very good agreement (κ=0.92) was observed between vaginal andMobley et al. Page 2Sex Transm Dis. Author manuscript; available in PMC 2013 September 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptendocervical specimens for TV detection, suggesting that the low agreement betweenspecimens 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 wasassociated 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 associationbetween cervicitis and MG-only detection by endocervical (OR 2.56, 95% CI 0.67-9.76) andvaginal specimens (OR 1.93, 95% CI 0.72-5.20), although the estimates were imprecisegiven the small numbers of patients in each group.In our study population, MG was detected more frequently than both NG and CT, and wascommonly isolated in women with other STIs. A higher prevalence of MG relative to CThas been observed by other investigators, [6, 15, 16] and lower estimates reported in otherstudies may reflect regional differences in MG prevalence.The vaginal swab specimen had a higher detection rate for MG than the endocervical swabspecimen. Although we were limited by not having an independent comparator assay withwhich to determine the sensitivity of the genital specimens, our MG TMA research assay islikely to be more sensitive than DNA-based PCR methods as it targets rRNA which ispresent in the cell in multiple copies as opposed to single-copy genes.[12] The higherdetection rate observed using vaginal versus endocervical specimens supports the findings ofother investigators.[11, 12, 16] This may reflect minimal host immune response to MGinfection in the vaginal epithelium, and thus greater bacterial survival in the vaginacompared to the endocervix, where the inflammatory response to MG by endocervicalepithelial cells is more robust.[19] This may also explain reported associations between MGand cervicitis,[3-5] but not vaginitis.[20]Although more cases of MG were detected using vaginal specimens, more than a quarter ofMG-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 twospecimens were combined.[11] However, testing from multiple specimens is not feasible inresource-limited settings such as public STI clinics. Self-collected vaginal swabs arepreferred by women and have higher sensitivities for STI detection than more invasiveforms of specimen collection.[12, 21-23] Therefore, the testing of a single self-collectedvaginal swab for NG, CT, TV and MG may result in the most cost-effective screeningrecommendation; however, the performance of self-collected vaginal specimens for MGdetection remains to be determined.In MG-positive women without other co-infections, young age and cervicitis were the onlypatient characteristics associated with MG detection. Being asymptomatic was associatedwith a 2-fold increased risk of detecting MG-only, but was only significant in bivariableanalyses; this finding which has been noted by others[24] suggests that MG infections inwomen may not be associated with specific urogenital symptoms. The association betweenyoung age and MG detection has been previously observed [25-27] and is likely mediated byboth biological (i.e. endocervical ectopy) and behavioral (i.e. number of sexual partners andinconsistent condom use) risk factors.[28, 29] The association between MG and cervicitis hasMobley et al. Page 3Sex Transm Dis. Author manuscript; available in PMC 2013 September 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptbeen reported by some investigators [3-6] but not others, [14, 15, 30] which likely stem fromthe wide discrepancy in how cervicitis is defined.In conclusion, NAATs using vaginal specimens for MG detection provide higher detectionrates than endocervical specimens, but would still miss a fourth of infections that weidentified using an IPS. Women with CT, NG and TV-infections have a high prevalence ofMG co-infection; however, MG prevalence is also high at 11.5% among women withoutother STIs. Young age and cervicitis were the only predictors significantly associated withMG-only infection in our study, and we found no associations with urogenital symptoms.Therefore, if NAATs for MG detection become commercially available, clinicians shouldconsider screening young asymptomatic women with cervicitis but recognize the potentiallimitations of the assay.AcknowledgmentsSources of Support: Supported by the National Institutes of Health/ National Institute for Allergy and InfectiousDisease grant 5 2 T32 AI 007001-34: Training in Sexually Transmitted Diseases and HIV (V.M.) and theSoutheastern Sexually Transmitted Infections Cooperative Research Center grant U19-AI031496 (M.M.H.)References1. Manhart LE. Has the time come to systematically test for Mycoplasma genitalium? Sex Transm Dis.2009; 36(10):607–8. [PubMed: 19734818]2. Haggerty CL, et al. Mycoplasma genitalium among women with nongonococcal, nonchlamydialpelvic inflammatory disease. Infect Dis Obstet Gynecol. 2006; 2006:30184. [PubMed: 17485798]3. Anagrius C, Lore B, Jensen JS. Mycoplasma genitalium: prevalence, clinical significance, andtransmission. Sex Transm Infect. 2005; 81(6):458–62. [PubMed: 16326846]4. Falk L, Fredlund H, Jensen JS. Signs and symptoms of urethritis and cervicitis among women withor without Mycoplasma genitalium or Chlamydia trachomatis infection. Sex Transm Infect. 2005;81(1):73–8. [PubMed: 15681728]5. Manhart LE, et al. Mucopurulent cervicitis and Mycoplasma genitalium. J Infect Dis. 2003; 187(4):650–7. [PubMed: 12599082]6. Gaydos C, et al. Mycoplasma genitalium as a contributor to the multiple etiologies of cervicitis inwomen attending sexually transmitted disease clinics. Sex Transm Dis. 2009; 36(10):598–606.[PubMed: 19704398]7. Cohen CR, et al. Association between Mycoplasma genitalium and acute endometritis. Lancet.2002; 359(9308):765–6. [PubMed: 11888591]8. Ross JD, Jensen JS. 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Comparison of first void urine and urogenital swab specimens for detection ofMycoplasma genitalium and Chlamydia trachomatis by polymerase chain reaction in patientsattending a sexually transmitted disease clinic. Sex Transm Dis. 2004; 31(8):499–507. [PubMed:15273584]14. Tosh AK, et al. Mycoplasma genitalium among adolescent women and their partners. J AdolescHealth. 2007; 40(5):412–7. [PubMed: 17448398]Mobley et al. Page 4Sex Transm Dis. Author manuscript; available in PMC 2013 September 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript15. Huppert JS, et al. Mycoplasma genitalium detected by transcription-mediated amplification isassociated with Chlamydia trachomatis in adolescent women. Sex Transm Dis. 2008; 35(3):250–4.[PubMed: 18490867]16. Casin I, et al. High prevalence of Mycoplasma genitalium in the lower genitourinary tract ofwomen attending a sexually transmitted disease clinic in Paris, France. Sex Transm Dis. 2002;29(6):353–9. [PubMed: 12035026]17. 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Mycoplasma genitalium Infection in Women Attending a Sexually Transmitted Infection Clinic: Diagnostic Specimen Type, Coinfections, and Predictors

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Mycoplasma genitalium Infection in Women Attending a Sexually Transmitted Infection Clinic: Diagnostic Specimen Type, Coinfections, and Predictors

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