Patricia A Totten

University of Washington Seattle, Seattle, Washington, United States

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Publications (63)265.56 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Ureaplasma urealyticum biovar 2 (UU-2), but not Ureaplasma parvum (UP), has been associated with non-gonococcal urethritis (NGU), but little is known about species-specific responses to standard therapies. We examined species-specific treatment outcomes and followed men with treatment failure for 9 weeks. From May 2007 to July 2011, men aged ≥16 attending a sexually transmitted disease (STD) clinic in Seattle, Washington, with NGU (urethral discharge or urethral symptoms plus ≥5 polymorphonuclear leucocytes /high-powered field) enrolled in a double-blind, randomised trial. Participants received active azithromycin (1 g) + placebo doxycycline or active doxycycline (100 mg twice a day ×7 days) + placebo azithromycin. Ureaplasma were detected in culture followed by species-specific PCR. Outcomes were assessed at 3, 6 and 9 weeks. At 3 weeks, men with persistent Ureaplasma detection received 'reverse therapy' (eg, active doxycycline if they first received active azithromycin). At 6 weeks, persistently positive men received moxifloxacin (400 mg×7 days). Of 490 men, 107 (22%) and 60 (12%) were infected with UU-2 and UP, respectively, and returned at 3 weeks. Persistent detection was similar for UU-2-infected men initially treated with azithromycin or doxycycline (25% vs 31%; p=0.53), but differed somewhat for men with UP (45% vs 24%; p=0.11). At 6 weeks, 57% of UU-2-infected and 63% of UP-infected men who received both drugs had persistent detection. Failure after moxifloxacin occurred in 30% and 36%, respectively. Persistent detection of UU-2 or UP was not associated with signs/symptoms of NGU. Persistent detection after treatment with doxycycline, azithromycin and moxifloxacin was common for UU and UP, but not associated with persistent urethritis. NCT00358462. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Sexually Transmitted Infections 01/2015; DOI:10.1136/sextrans-2014-051859 · 3.08 Impact Factor
  • Raul Burgos, Patricia A. Totten
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    ABSTRACT: The human pathogen Mycoplasma genitalium employs homologous recombination to generate antigenic diversity in the immunodominant MgpB and MgpC proteins. Only recently, some of the molecular factors involved in this process have been characterized, but nothing is known about its regulation. Here, we show that M. genitalium expresses N-terminally truncated RecA isoforms via alternative translation initiation, but only the full-length protein is essential for gene variation. We also demonstrate that overexpression of MG428 positively regulates the expression of recombination genes, including recA, ruvA, ruvB and ORF2, a gene of unknown function co-transcribed with ruvAB. The coordinated induction of these genes correlated with an increase of mgpBC gene variation. In contrast, cells lacking MG428 were unable to generate variants despite expressing normal levels of RecA. Similarly, deletion analyses of the recA upstream region defined sequences required for gene variation without abolishing RecA expression. The requirement of these sequences is consistent with the presence of promoter elements associated with MG428-dependent recA induction. Sequences upstream of recA also influence the relative abundance of RecA isoforms, possibly through translational regulation. Overall, these results suggest that MG428 is a positive regulator of recombination and that precise control of recA expression is required to initiate mgpBC variation.
    Molecular Microbiology 08/2014; 94(2). DOI:10.1111/mmi.12760 · 5.03 Impact Factor
  • Raul Burgos, Patricia A Totten
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    ABSTRACT: Mycoplasma genitalium is an emerging sexually transmitted pathogen associated with reproductive tract disease in men and women, and can persist for months to years despite the development of a robust antibody response. Mechanisms that may contribute to persistence in vivo include phase and antigenic variation of the MgpB and MgpC adhesins. These processes occur by segmental recombination between discrete variable regions within mgpB and mgpC and multiple archived donor sequences termed MgPa repeats (MgPars). The molecular factors governing mgpB/C variation are poorly understood and obscured by the paucity of recombination genes conserved in the M. genitalium genome. Recently, we demonstrated the requirement for RecA using a qPCR assay developed to measure mgpB/C-MgPar recombination. Here, we expand these studies by examining the role of M. genitalium ruvA and ruvB homologs. Deletion of ruvA and ruvB impaired the ability to generate mgpB/C phase and sequence variants, and these deficiencies could be complemented with wild-type copies, including the ruvA gene from Mycoplasma pneumoniae. In contrast, ruvA and ruvB deletions did not affect the sensitivity to UV irradiation, reinforcing our previous findings that the recombinational repair pathway plays a minor role in M. genitalium. RT-PCR and primer extension analyses also revealed a complex transcriptional organization of the RuvAB system of M. genitalium, which is co-transcribed with two novel open reading frames (termed ORF1 and ORF2 herein) conserved only in M. pneumoniae. These findings suggest that these novel ORFs may play a role in recombination in these two closely related bacteria.
    Journal of bacteriology 02/2014; DOI:10.1128/JB.01385-13 · 2.69 Impact Factor
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    ABSTRACT: Doxycycline, one of two recommended therapies for non-gonococcal urethritis (NGU), consists of a 7-day course of therapy (100 mg BID). Since suboptimal adherence may contribute to poor treatment outcomes, we examined the association between self-reported imperfect adherence to doxycycline and clinical and microbiologic failure among men with NGU. Men aged ≥16 years with NGU attending a Seattle, WA, sexually transmitted diseases clinic were enrolled in a double-blind, parallel-group superiority trial from January 2007 to July 2011. Men were randomised to active doxycycline/placebo azithromycin or placebo doxycycline/active azithromycin. Imperfect adherence was defined as missing ≥1 dose in 7 days. Urine was tested for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Ureaplasma urealyticum-biovar 2 (UU-2) using nucleic acid amplification tests. Clinical failure (symptoms and ≥5 PMNs/HPF or discharge) and microbiologic failure (positive tests for CT, MG, and/or UU-2) were determined after 3 weeks. 184 men with NGU were randomised to active doxycycline and provided data on adherence. Baseline prevalence of CT, MG and UU-2 was 26%, 13% and 27%, respectively. 28% of men reported imperfect adherence, and this was associated with microbiologic failure among men with CT (aRR=9.33; 95% CI 1.00 to 89.2) and UU-2 (aRR=3.08; 95% CI 1.31 to 7.26) but not MG. Imperfect adherence was not significantly associated with clinical failure overall or for any specific pathogens, but it was more common among imperfectly adherent men with CT (aRR=2.63; 0.93-7.41, p=0.07). Adherence may be important for microbiologic cure of select pathogens. Factors other than adherence should be considered for CT-negative men with persistent NGU.
    Sexually transmitted infections 10/2013; 90(1). DOI:10.1136/sextrans-2013-051174 · 3.08 Impact Factor
  • Sexually Transmitted Infections 07/2013; 89(Suppl 1):A29-A29. DOI:10.1136/sextrans-2013-051184.0091 · 3.08 Impact Factor
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    ABSTRACT: Mycoplasma genitalium is a sexually transmitted pathogen associated with several acute and chronic reproductive tract disease syndromes in men and women. To evaluate the suitability of a pigtailed macaque model of M. genitalium infection, we inoculated a pilot animal with M. genitalium strain G37 in the uterine cervix and in salpingeal pockets generated by transplanting autologous Fallopian tube tissue subcutaneously. Viable organisms were recovered throughout the eight-week experiment in cervicovaginal specimens and up to two weeks post-infection in salpingeal pockets. Humoral and cervicovaginal antibodies reacting to MgpB were induced post-inoculation and persisted throughout the infection. The immunodominance of the MgpB adhesin and the accumulation of mgpB sequence diversity previously observed in persistent human infections prompted us to evaluate sequence variation in this animal model. We found that after eight weeks of infection, sequences within mgpB variable region B were replaced by novel sequences generated by reciprocal recombination with an archived variant sequence located elsewhere on the chromosome. In contrast, mgpB region B of the same inoculum propagated for eight weeks in vitro remained unchanged. Notably, serum IgG reacted strongly with a recombinant protein spanning MgpB region B of the inoculum, while reactivity to a recombinant protein representing the Week 8 variant was reduced, suggesting antibodies were involved in the clearance of bacteria expressing the original infecting sequence. Together these results suggest that the pigtailed macaque is a suitable model to study M. genitalium pathogenesis, antibody-mediated selection of antigenic variants in vivo, and immune escape.
    Infection and immunity 06/2013; DOI:10.1128/IAI.01322-12 · 4.16 Impact Factor
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    ABSTRACT: Background. Azithromycin or doxycycline is recommended for nongonococcal urethritis (NGU). Recent evidence suggests their efficacy has declined. We compared azithromycin and doxycycline in men with NGU, hypothesizing that azithromycin was more effective than doxycycline.Methods. From January 2007-July 2011, English-speaking males ≥16 years, attending a sexually transmitted diseases clinic in Seattle, Washington with NGU (visible urethral discharge or ≥5 PMNs/HPF) were eligible for this double-blind, parallel-group superiority trial ( (NCT00358462)). Participants received active azithromycin (1g)+placebo doxycycline or active doxycycline (100mg bidx7d)+placebo azithromycin. Urine was tested for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Ureaplasma urealyticum-biovar 2 (UU-2) and Trichomonas vaginalis (TV) using nucleic acid amplification tests. Clinical cure (<5 PMNs/HPF with or without urethral symptoms and absence of discharge) and microbiologic cure (negative tests for CT, MG, and/or UU-2) were determined after 3 weeks.Results. Of 606 men, 304 were randomized to azithromycin and 302 to doxycycline. CT, MG, TV and UU-2 were detected in 24%, 13%, 2%, and 23%, respectively. In modified intent-to-treat analyses, 80% (172 of 216) (95% confidence interval 74-85%) receiving azithromycin and 76% (157 of 206) (70-82%) receiving doxycycline experienced clinical cure (p=0.40). In pathogen-specific analyses, clinical cure did not differ by arm, nor did microbiologic cure differ for CT (86% versus 90%, p=0.56), MG (40% versus 30%, p=0.41), or UU-2 (75% versus 70%, p=0.50). No unexpected adverse events occurred.Conclusions. Clinical and microbiologic cure of NGU were somewhat low and there was no significant difference between azithromycin and doxycycline. M. genitalium treatment failure was extremely common.
    Clinical Infectious Diseases 12/2012; 56(7). DOI:10.1093/cid/cis1022 · 9.42 Impact Factor
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    ABSTRACT: An international multilaboratory collaborative study was conducted to develop standard media and consensus methods for the performance and quality control of antimicrobial susceptibility testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum using broth microdilution and agar dilution techniques. A reference strain from the American Type Culture Collection was designated for each species, which was to be used for quality control purposes. Repeat testing of replicate samples of each reference strain by participating laboratories utilizing both methods and different lots of media enabled a 3- to 4-dilution MIC range to be established for drugs in several different classes, including tetracyclines, macrolides, ketolides, lincosamides, and fluoroquinolones. This represents the first multilaboratory collaboration to standardize susceptibility testing methods and to designate quality control parameters to ensure accurate and reliable assay results for mycoplasmas and ureaplasmas that infect humans.
    Journal of clinical microbiology 08/2012; 50(11):3542-7. DOI:10.1128/JCM.01439-12 · 4.23 Impact Factor
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    ABSTRACT: Mycoplasma genitalium, a sexually transmitted human pathogen, encodes MgpB and MgpC adhesins that undergo phase and antigenic variation through recombination with archived 'MgPar' donor sequences. The mechanism and molecular factors required for this genetic variation are poorly understood. In this study, we estimate that sequence variation at the mgpB/C locus occurs in vitro at a frequency of > 1.25 × 10(-4) events per genome per generation using a quantitative anchored PCR assay. This rate was dramatically reduced in a recA deletion mutant and increased in a complemented strain overexpressing RecA. Similarly, the frequency of haemadsorption-deficient phase variants was reduced in the recA mutant, but restored by complementation. Unlike Escherichia coli, inactivation of recA in M. genitalium had a minimal effect on survival after exposure to mitomycin C or UV irradiation. In contrast, a deletion mutant for the predicted nucleotide excision repair uvrC gene showed growth defects and was exquisitely sensitive to DNA damage. We conclude that M. genitalium RecA has a primary role in mgpB/C-MgPar recombination leading to antigenic and phase variation, yet plays a minor role in DNA repair. Our results also suggest that M. genitalium possesses an active nucleotide excision repair system, possibly representing the main DNA repair pathway in this minimal bacterium.
    Molecular Microbiology 06/2012; 85(4):669-83. DOI:10.1111/j.1365-2958.2012.08130.x · 5.03 Impact Factor
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    ABSTRACT: Ureaplasmas have been inconsistently associated with nongonococcal urethritis (NGU). We evaluated the association of the newly differentiated species Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) with NGU using 2 separate control groups. Case patients were men who attended a sexually transmitted disease (STD) clinic in Seattle, Washington, during the period 2007-2009 with NGU (defined as visible urethral discharge and/or ≥5 polymorphonuclear neutrophils per high-powered field; n = 329). Control subjects were STD clinic attendees (n = 191) and emergency department (ED) attendees (n = 193) without NGU. Polymerase chain reaction assays detected UU and UP in ureaplasma culture-positive urine. Multivariable logistic regression was used to assess the associations of UU and UP with NGU. UU was only marginally associated with NGU in aggregate multivariable analyses, irrespective of control group (adjusted odds ratio [aOR](STD-control), 1.6 [95% confidence interval {CI}, 0.9-2.8]; aOR(ED-control), 1.7 [95% CI, 0.97-3.0]). This association was significantly stronger when analyses were restricted to men with fewer lifetime sex partners (<10 vaginal partners: aOR(STD-control), 2.9 [95% CI, 1.2-6.7]; aOR(ED-control), 3.2 [95% CI, 1.3-7.6]; <5 vaginal partners: aOR(STD-control), 6.2 [95% CI, 1.8-21.0]; aOR(ED-control), 5.2 [95% CI, 1.3-20.2]). UP was not positively associated with NGU overall or among subgroups. The absence of an association of UU with NGU among men with more lifetime sex partners suggests that adaptive immunity may attenuate the clinical manifestation of UU infection. Similar relationships were not observed with UP, which suggests that it is not a urethral pathogen.
    The Journal of Infectious Diseases 10/2011; 204(8):1274-82. DOI:10.1093/infdis/jir517 · 5.85 Impact Factor
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    ABSTRACT: Mycoplasma genitalium-reactive cervicovaginal IgA and IgG antibodies were detected in 51.9% and 70.4% of 27 infected women and 22.2% and 18.5% of 27 uninfected controls, respectively. The predominance of MgpB- and MgpC-reactive antibodies at the site of infection is consistent with their hypothesized role in selecting antigenic variants during persistent infection.
    Clinical and vaccine Immunology: CVI 08/2011; 18(10):1783-6. DOI:10.1128/CVI.05174-11 · 2.37 Impact Factor
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    ABSTRACT: Nongonococcal urethritis (NGU) is common, yet up to 50% of cases have no defined etiology. The extent to which risk profiles and clinical presentations of pathogen-associated and idiopathic cases differ is largely unknown. Urethral swabs and urine specimens were collected from 370 NGU treatment trial participants who sought care at a sexually transmitted disease clinic in Seattle, WA from 2007 to 2009 and had a visible urethral discharge and/or microscopic evidence of urethral inflammation assessed by Gram-stain (≥5 polymorphonuclear leukocytes per high-powered field [PMNs/HPF]). Neisseria gonorrhoeae, Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV), and Ureaplasma urealyticum (UU) were detected in urine, using nucleic acid amplification tests. Cases negative for all assessed pathogens were considered idiopathic. Bivariate and multivariate analyses identified clinical, sociodemographic, and behavioral factors associated with detection of specific pathogens. After excluding 3 participants with gonococcal infection, pathogens were detected in only 50.7% of the 367 eligible cases: CT in 22.3%, MG in 12.5%, TV in 2.5%, and UU in 24.0%, with multiple pathogens detected in 9.5%. In all, 3.5% of cases were negative for CT, MG, and TV but lacked speciated ureaplasma results. The remaining cases (45.8%) were considered idiopathic. Pathogen detection was associated with young age, black race, risky sexual behaviors, cloudy or purulent discharge, and visible discharge plus≥5 PMNs/HPF. In contrast, idiopathic cases were more likely to report prior NGU, were older and less likely to be black, or have an abnormal urethral discharge on examination, compared to all other cases. These cases were not associated with any high risk behaviors. NGU is a heterogeneous condition. Pathogen detection was associated with a variety of traditional risk factors and clinical features; whereas, idiopathic cases tended to be diagnosed among lower-risk men.
    Sexually transmitted diseases 03/2011; 38(3):180-6. DOI:10.1097/OLQ.0b013e3182040de9 · 2.58 Impact Factor
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    ABSTRACT: Neisseria gonorrhoeae and Chlamydia trachomatis are characterized by different risk factors, thus control strategies for each also differ. In contrast, risk factors for Mycoplasma genitalium have not been well characterized. Between 2000 and 2006, 1090 women ages 14 to 45 attending the Public Health-Seattle & King County Sexually Transmitted Diseases Clinic in Seattle, WA, underwent clinical examination and computer-assisted survey interview. M. genitalium was detected by transcription mediated amplification from self-obtained vaginal swab specimens. C. trachomatis and N. gonorrhoeae were detected by culture from cervical swab specimens. Prevalent M. genitalium infection was detected in 84 women (7.7%), C. trachomatis in 63 (5.8%), and N. gonorrhoeae in 26 (2.4%). Age <20 and nonwhite race were associated with increased risk for all 3 organisms. In addition, risk for M. genitalium was higher for women with a black partner (adjusted odds ratio [AOR]: 3.4; 95% confidence interval = 1.83-6.29), those never married (AOR: 2.6; 1.08-6.25), using Depo-Provera (AOR: 2.3; 1.19-4.46), and smoking (AOR: 1.7; 1.03-2.83). Drug use, history of STI in the past year, ≤high school education, meeting and having intercourse the same day, anal sex, douching, and hormonal contraception were associated with N. gonorrhoeae or C. trachomatis, but not with M. genitalium. Number of partners was not associated with any of the 3 organisms. The limited number of risk factors for prevalent infection common to all 3 pathogens suggests that M. genitalium may circulate in different sexual networks than N. gonorrhoeae or C. trachomatis. The predominance of sociodemographic risk factors for M. genitalium, rather than high-risk sexual behaviors, suggests broad-based testing may be the most effective control strategy.
    Sexually transmitted diseases 12/2010; 37(12):777-83. DOI:10.1097/OLQ.0b013e3181e8087e · 2.58 Impact Factor
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    ABSTRACT: To assess the role of Ureaplasma urealyticum and Ureaplasma parvum in patients with non-gonococcal urethritis (NGU) using specimens from a previously reported study of NGU. Species-specific PCR assays for U urealyticum and U parvum were used to detect these organisms in specimens from men enrolled in a case-control study based in a Seattle STD clinic in order to evaluate their association with NGU. Urethritis was defined by clinical examination and the presence of inflammation on Gram stained smear. Controls had normal examination findings and no evidence of inflammation on Gram stain smear or by the leucocyte esterase test. U urealyticum was detected in 26% (31/119) of cases and 16% (19/117) of controls, resulting in an association with NGU (adjusted odds ratio (aOR)=2.3, 95% CI 1.04 to 4.9) after adjusting for age, race, history of prior urethritis and other NGU pathogens (Chlamydia trachomatis, Mycoplasma genitalium). The association of U urealyticum and NGU was strongest in white men <28 years of age (OR=5.4, 95% CI 1.3 to 22.2). U parvum was detected in 14% (17/119) cases and 31% (36/117 controls) and thus was negatively associated with NGU (aOR=0.4, 95% CI 0.2 to 0.8). The prevalence of U urealyticum (16%) in controls was higher than that of C trachomatis (3.4%) or M genitalium (4.3%, p<0.05, each comparison). Unlike U parvum, U urealyticum was associated with urethritis. The strong effect in younger white men and high rates in controls may suggest variability in virulence among U urealyticum strains or in host innate or acquired immunity.
    Sexually transmitted infections 05/2010; 86(4):271-5. DOI:10.1136/sti.2009.040394 · 3.08 Impact Factor
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    ABSTRACT: Mycoplasma genitalium is associated with cervicitis and pelvic inflammatory disease in nonpregnant women. We investigated associations between cervical M genitalium, demographic and behavioral risk factors for sexually transmitted infection and preterm birth among low-income Peruvian women. This case-control study, conducted at the Instituto Nacional Materno Perinatal, Lima, Peru, included 661 cases with a spontaneous preterm birth at <37 weeks and 667 controls who delivered at >or=37 weeks. Within 48 hours after delivery, subjects underwent interviews, medical record review, and collection of cervicovaginal specimens for M. genitalium, Chlamydia trachomatis, and Neisseria gonorrhoeae by nucleic acid amplification testing, and Trichomonas vaginalis by culture. Odds ratios and 95% confidence intervals were calculated for associations between M. genitalium, other genital infections and risk factors, and preterm birth. Multivariable logistic regression was used to adjust for potential confounders. Cervical M. genitalium was detected in 3% of subjects and was significantly associated with C. trachomatis infection (P < 0.001) and preterm birth (4% vs. 2%; adjusted odds ratio: 2.5, 95% confidence interval: 1.2-5.0, P = 0.014), and marginally associated with T. vaginalis (P = 0.05). M. genitalium detection was also associated with younger maternal age (P = 0.003) but not with other risk factors for preterm birth. The association between cervical M. genitalium detection and preterm birth remained significant after adjustment for maternal age and coinfection with C. trachomatis or T. vaginalis. Cervical M. genitalium detection was independently associated with younger maternal age and preterm birth, suggesting that this organism may be an infectious correlate of spontaneous preterm birth.
    Sexually transmitted diseases 02/2010; 37(2):81-5. DOI:10.1097/OLQ.0b013e3181bf5441 · 2.58 Impact Factor
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    ABSTRACT: Mycoplasma genitalium has been identified as a cause of pelvic inflammatory disease (PID), a clinical syndrome associated with inflammation of the female upper genital tract and serious reproductive sequelae. As the demographic, behavioural and sexual risk profile of women with M genitalium-associated PID is not well understood, the characteristics of M genitalium-infected women presenting with clinically suspected PID were investigated. Data from 586 participants in the PID Evaluation and Clinical Health Study were analysed. Demographic, sexual history and behavioural characteristics, including age, race, marital status, education level, sexual activity, number of sexual partners, history of sexually transmitted infection (STI), bacterial vaginosis and PID, contraception use, oral and anal sex, age at sexual debut, douching practices and drug, alcohol and tobacco use, were compared between 88 women testing positive and 498 women testing negative for M genitalium by PCR in the cervix and/or endometrium. Twenty-two women with M genitalium mono-infections were compared with 172 women who tested positive for Neisseria gonorrhoeae by culture and/or Chlamydia trachomatis by PCR. Age under 25 years, douching two or more times per month and smoking were independently associated with M genitalium. Women with M genitalium mono-infections were significantly less likely to be African-American (59.1% vs 86.0%, p = 0.001) than women with N gonorrhoeae and/or C trachomatis. Women infected with M genitalium had some characteristics commonly associated with PID and other STI. The demographic, sexual and behavioural characteristics of M genitalium-positive women were similar to women with chlamydial and/or gonococcal PID.
    Sexually transmitted infections 08/2009; 86(1):29-31. DOI:10.1136/sti.2009.037721 · 3.08 Impact Factor
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    ABSTRACT: Women with pelvic inflammatory disease (PID) often present with a spectrum of symptoms. The characteristics of nongonococcal, nonchlamydial PID have not been well described. Our objective was to examine the characteristics of Mycoplasma genitalium infection among women with clinically suspected PID. We evaluated 722 women who were enrolled in the PID Evaluation and Clinical Health study. Women with M. genitalium monoinfection were compared with women with Neisseria gonorrhoeae monoinfection or Chlamydia trachomatis monoinfection. Compared with women with gonococcal PID, women with M. genitalium infection were less likely to have elevated systemic inflammatory markers, including an erythrocyte sedimentation rate >15 mm/h (5 [22.7%] of 22 patients vs. 45 [60.8%] of 74 patients; P = .002), a white blood cell count >10,000 cells/mL (4 [28.6%] of 14 patients vs. 42 [64.6%] of 65 patients; (P = .018), and an oral temperature > or =38.3 degrees C (0 [0.0%] of 22 patients vs. 10 [13.9%] of 72 patients; (P = .001). In addition, they were less likely to present with mucopurulent cervicitis (9 [47.4%] of 19 patients vs. 60 [83.3%] of 72 patients; P = .001), elevated vaginal pH (P = .018), and high pelvic pain score (P = .014). In contrast, women with chlamydial PID had signs and symptoms that were similar to those in women with M. genitalium infection. Because symptoms might be mild, women with M. genitalium infection might not seek PID treatment. Further studies are needed to assess the potential reproductive tract sequelae of M. genitalium infection of the upper genital tract.
    Clinical Infectious Diseases 12/2008; 48(1):41-7. DOI:10.1086/594123 · 9.42 Impact Factor
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    ABSTRACT: As the aetiology of bacterial vaginosis (BV) is not well understood, this study sought to determine the relationships between several fastidious microbes, BV and selected clinical characteristics of BV. Endometrial and cervical specimens from 50 women with non-gonococcal, non-chlamydial endometritis were tested for Leptotrichia sanguinegens/amnionii, Atopobium vaginae, bacterial vaginosis-associated bacteria 1 (BVAB1), Ureaplasma urealyticum biovar 2 (UU-2) and Ureaplasma parvum using PCR. BV was categorised using Nugent's and Amsel's criteria. Odds ratios (OR) adjusted for age and race were estimated using multivariable logistic regression. Although elevated pH was a universal feature, other BV characteristics differed by pathogen, suggesting variable clinical presentation. Only UU-2 was strongly associated with vaginal discharge, but a positive whiff test and a 20% or greater classification of epithelial cells as clue cells were more common among women with L sanguinegens/amnionii, A vaginae and BVAB1. For each of these bacteria, there were trends towards associations with BV defined by Amsel's criteria (L sanguinegens/amnionii OR 2.9, 95% CI 0.5 to 15.7; A vaginae OR 2.6, 95% CI 0.6 to 11.4; BVAB1 OR 5.7, 95% CI 1.0 to 31.1) and significant associations with BV defined by Gram stain (L sanguinegens/amnionii OR 17.7, 95% CI 2.8 to 113.0; A vaginae OR 19.2, 95% CI 3.7 to 98.7; BVAB1 OR 21.1, 95% CI 2.2 to 198.5). L sanguinegens/amnionii, A vaginae and BVAB1 are associated with clinical characteristics consistent with BV and BV defined by Nugent's and Amsel's criteria. These fastidious bacteria may cause unrecognised infection, as none was associated with abnormal vaginal discharge.
    Sexually transmitted infections 12/2008; 85(4):242-8. DOI:10.1136/sti.2008.032821 · 3.08 Impact Factor
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    ABSTRACT: As Mycoplasma genitalium is associated with pelvic inflammatory disease (PID), we examined the efficacy of a commonly used PID antimicrobial in treating M genitalium upper genital tract infection. In the PID Evaluation and Clinical Health study of inpatient versus outpatient treatment, 682 women treated with cefoxitin and doxycycline for clinically suspected PID had stored cervical and endometrial specimens available for analysis. In the current sub study, we compared baseline endometritis, short term treatment failure (continued endometritis and pelvic pain 30 days following treatment) and sequelae among women with and without M genitalium, identified using PCR. Endometrial M genitalium was associated with baseline endometritis (adjusted OR 3.0, 95% CI 1.5 to 6.1). Among women with a positive baseline M genitalium test, 41% tested positive again 30 days following treatment. Women testing positive compared to those testing negative for M genitalium at baseline had an increased risk of short-term treatment failure (RR 4.6, 95% CI 1.1 to 20.1). Rates of sequelae, including infertility (22%), recurrent PID (31%) and chronic pelvic pain (42%), were high among women testing positive for endometrial M genitalium at baseline. There was a non-significant trend towards increased infertility, chronic pelvic pain and recurrent PID, and decreased pregnancy and live birth following M genitalium infection. M genitalium is associated with endometritis and short-term PID treatment failure. Cefoxitin and doxycycline, a Centers for Disease Control and Prevention recommended PID treatment regimen, is ineffective for the treatment of M genitalium upper genital tract infection.
    Sexually transmitted infections 05/2008; 84(5):338-42. DOI:10.1136/sti.2008.030486 · 3.08 Impact Factor
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    ABSTRACT: We assessed the relationship between infection with Mycoplasma genitalium, an emerging sexually transmitted pathogen, and cervical shedding of human immunodeficiency virus (HIV)-1 DNA among 303 HIV-1-positive Kenyan women. HIV-1 shedding was detected by qualitative polymerase chain reaction (PCR) in 154 women (51%); M. genitalium was detected by qualitative PCR in 52 (17%), and organism burden was determined by quantitative PCR. Women with high M. genitalium organism burdens (more than the median of 3195 genomes/mL) were 3-fold more likely to shed HIV-1 DNA than were M. genitalium-negative women (adjusted OR, 2.9 [95% confidence interval, 1.1-7.6]), yet this did not appear to be mediated by traditional measures of cervical inflammation (elevated polymorphonuclear leukocyte count).
    The Journal of Infectious Diseases 04/2008; 197(5):733-6. DOI:10.1086/526501 · 5.78 Impact Factor

Publication Stats

2k Citations
265.56 Total Impact Points


  • 1990–2015
    • University of Washington Seattle
      • • Department of Medicine
      • • Department of Global Health
      • • Division of Allergy and Infectious Diseases
      • • Department of Microbiology
      Seattle, Washington, United States
  • 2012
    • George Washington University
      • Department of Epidemiology
      Washington, Washington, D.C., United States
  • 2005–2007
    • University of California, San Francisco
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      San Francisco, CA, United States
  • 2006
    • CSU Mentor
      Long Beach, California, United States
  • 1998
    • Centers for Disease Control and Prevention
      • Division for Heart Disease and Stroke Prevention
      Atlanta, Michigan, United States
  • 1996
    • Hôpital St-Boniface Hospital
      Winnipeg, Manitoba, Canada
  • 1991
    • University of Florida
      • Department of Medicine
      Gainesville, FL, United States