Catriona S. Bradshaw

High Recurrence Rates of Bacterial Vaginosis over the Course of 12 Months after Oral Metronidazole Therapy and Factors Associated with Recurrence

BACKGROUND We wished to determine recurrences of bacterial vaginosis (BV) after treatment over the course of 12 months and to establish factors associated with recurrence. METHODS Women with symptomatic BV (a Nugent score [NS] of 7-10 or of 4-6 with >or=3 Amsel criteria) were enrolled. BV was treated with 400 mg of oral metronidazole twice a day for 7 days. Participants completed a questionnaire and vaginal swabs were collected at 1, 3, 6, and 12 months; the study end point was an NS of 7-10. RESULTS A total of 121 (87%) women with an NS of 7-10 and 18 (13%) with an NS of 4-6 and >or=3 Amsel criteria were enrolled; 130 (94%) returned >or=1 vaginal samples. Sixty-eight women (58% [95% confidence interval {CI}, 49%-66%]) had a recurrence of BV (NS 7-10), and 84 (69% [95% CI, 61%-77%]) had a recurrence of abnormal vaginal flora (NS 4-10) by 12 months. A past history of BV, a regular sex partner throughout the study, and female sex partners were significantly associated with recurrence of BV and abnormal vaginal flora by multivariate analysis; the use of hormonal contraception had a negative association with recurrence. CONCLUSION Current recommended treatment is not preventing the recurrence of BV or abnormal vaginal flora in the majority of women; factors associated with recurrence support a possible role for sexual transmission in the pathogenesis of recurrent BV.

Rapid decline in presentations of genital warts after the implementation of a national quadrivalent human papillomavirus vaccination programme for young women.

Objective: This study aimed to determine if the Australian human papillomavirus (HPV) vaccination programme has had a population impact on presentations of genital warts. Methods: Retrospective study comparing the proportion of new clients with genital warts attending Melbourne Sexual Health Centre (MSHC) from January 2004 to December 2008. Australia provided free quadrivalent HPV vaccine to 12–18-year-old girls in a school-based programme from April 2007, and to women 26 years and younger through general practices from July 2007. Results: 36 055 new clients attended MSHC between 2004 and 2008 and genital warts were diagnosed in 3826 (10.6%; 95% CI 10.3 to 10.9). The proportion of women under 28 years with warts diagnosed decreased by 25.1% (95% CI 30.5% to 19.3%) per quarter in 2008. Comparing this to a negligible increase of 1.8% (95% CI 0.2% to 3.4%) per quarter from the start of 2004 to the end of 2007 also in women under 28 years generates strong evidence of a difference in these two trends (p<0.001). There was no evidence of a difference in trend for the quarterly proportions before and after the end of 2007 for any other subgroup, and on only one occasion was there strong evidence of a trend different to zero, for heterosexual men in 2008 in whom the average quarterly change was a decrease of 5% (95% CI 0.5% to 9.4%; p = 0.031). Conclusions: The data suggest that a rapid and marked reduction in the incidence of genital warts among vaccinated women may be achievable through an HPV vaccination programme targeting women, and supports some benefit being conferred to heterosexual men.

The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme

Background Australia provided free quadrivalent human papillomavirus vaccines to 12–18-year-old girls and women aged ≤26 years from mid-2007 until the end of 2009. After this time, only girls aged 12–13 years had access to free vaccines. Methods Before and after the study, of the proportion of new patients attending Melbourne Sexual Health Centre from mid-2004 to mid-2011, diagnosed with genital warts (GW) by risk group. Results From July 2004 to June 2011, 52 454 new patients were seen at Melbourne Sexual Health Centre and 5021 (9.6%, 95% CI 9.3% to 9.8%) were diagnosed with GW. From July 2004 to June 2007, the proportions with GW either increased or did not change in all groups. Comparing the two 12-month periods of 2007/2008 and 2010/2011, GW declined in women under 21 years from 18.6% to 1.9% and in heterosexual men under 21 years from 22.9% to 2.9%. The ORs per year for diagnosis of GW adjusted for number of sexual partners from July 2007 until June 2011 in women and heterosexual men <21 years were 0.44 (95% CI 0.32 to 0.58) and 0.42 (95% CI 0.31 to 0.60), respectively. There was no significant change in GW in women ≥30 years (OR 0.97, 95% CI 0.84 to 1.12), heterosexual men ≥30 years (OR 0.97, 95% CI 0.89 to 1.06) or in homosexual men (OR 0.95, 95% CI 0.85 to 1.07). Conclusion The dramatic decline and near disappearance of GW in women and men under 21 years of age, 4 years after commencing this programme, suggest that the basic reproductive rate has fallen below one.

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

BACKGROUND The purpose of the present study was to determine pathogens and behaviors associated with nongonococcal urethritis (NGU) and the usefulness of the urethral smear in predicting the presence of pathogens. METHODS We conducted a case-control study of men with and without symptoms of NGU. Sexual practices were measured by questionnaire. First-stream urine was tested for Chlamydia trachomatis, Mycoplasma genitalium, Ureaplasma parvum, U. urealyticum, herpes simplex virus (HSV)-1, HSV-2, adenoviruses, and Gardnerella vaginalis by polymerase chain reaction. RESULTS C. trachomatis (20%), M. genitalium (9%), adenoviruses (4%), and HSV-1 (2%) were more common in cases with NGU (n = 329) after age and sexual risk were adjusted for (P< or =.01); U. urealyticum, U. parvum, and G. vaginalis were not. Infection with adenoviruses or HSV-1 was associated with distinct clinical features, oral sex, and male partners, whereas infection with M. genitalium or C. trachomatis was associated with unprotected vaginal sex. Oral sex was associated with NGU in which no pathogen was detected (P < or = .001). Fewer than 5 polymorphonuclear leukocytes (PMNLs) per high-power field (HPF) on urethral smear were present in 32%, 37%, 38%, and 44% of cases with C. trachomatis, M. genitalium, adenoviruses, and HSV, respectively. CONCLUSION We identified adenoviruses and HSV-1 as significant causes of NGU with distinct clinical and behavioral characteristics and highlighted the association between insertive oral sex and NGU. A urethral PMNL count of > or =5 PMNLs/HPF is not sufficiently sensitive to exclude pathogens in men with urethral symptoms.

Sexual Risk Factors and Bacterial Vaginosis: A Systematic Review and Meta-Analysis

We performed a systematic review and meta-analysis of the association between sexual risk factors and bacterial vaginosis (BV). Forty-three studies reported new or multiple sexual partners and condom use relative to prevalent, incident, or recurrent BV. The summary estimate of the relative risk for the association between BV new or multiple male partners was 1.6 (95% confidence interval, 1.5-1.8), between BV and any female partners was 2.0 (95% confidence interval, 1.7-2.3), and between BV and condom use was 0.8 (95% confidence interval, 0.8-0.9). This review is the first to summarize available observational data for BV. It shows that BV is significantly associated with sexual contact with new and multiple male and female partners and that decreasing the number of unprotected sexual encounters may reduce incident and recurrent infection. Investigation of sexual transmission of BV is limited by the absence of a clear microbiological etiology; however, we have shown that the epidemiological profile of BV is similar to that of established sexually transmitted infections.

Azithromycin Treatment Failure in Mycoplasma genitalium–Positive Patients with Nongonococcal Urethritis Is Associated with Induced Macrolide Resistance

BACKGROUND Mycoplasma genitalium is a common cause of nongonococcal urethritis. Treatment trials have shown that doxycycline is inefficient, whereas a 5-day course of azithromycin eradicates the bacterium from 95% of infected men. The aim of the study was to establish the reason for the occasional treatment failures. METHODS Seven M. genitalium strains isolated from men who experienced azithromycin treatment failure were tested for in vitro susceptibility to macrolides with use of a cell culture-based method. The genetic basis for the drug resistance was established by sequencing parts of the 23S ribosomal RNA gene and the genes encoding the L4 and L22 proteins. Nine sets of specimens obtained before and after treatment from patients who experienced azithromycin treatment failure were examined with use of sequencing of polymerase chain reaction products. RESULTS The 7 strains that were isolated from patients who experienced treatment failure with azithromycin had minimum inhibitory concentrations >8 microg/mL for azithromycin and erythromycin. Three different mutations at positions 2058 and 2059 (Escherichia coli numbering) in region V of the 23S rRNA gene were found. Of the 9 patients with specimens obtained before and after treatment, only 2 had an initial specimen in which the mutation was present, indicating that drug resistance was induced as the result of an inappropriate dosage of azithromycin. CONCLUSION Development of macrolide resistance was shown to correlate with subsequent azithromycin treatment failure. The genetic basis for the drug resistance was shown to be mutations in region V of the 23S rRNA gene, which is well described in other Mollicutes. These findings raise concern about the use of single-dose azithromycin treatment of nongonococcal urethritis of unknown etiology.

Azithromycin failure in Mycoplasma genitalium urethritis.

We report significant failure rates (28%, 95% confidence interval 15%–45%) after administering 1 g azithromycin to men with Mycoplasma genitalium–positive nongonococcal urethritis. In vitro evidence supported reduced susceptibility of M. genitalium to macrolides. Moxifloxacin administration resulted in rapid symptom resolution and eradication of infection in all cases. These findings have implications for management of urethritis.

The Association of Atopobium vaginae and Gardnerella vaginalis with Bacterial Vaginosis and Recurrence after Oral Metronidazole Therapy

BACKGROUND We investigated associations between Atopobium vaginae and bacterial vaginosis (BV) and the role that A. vaginae plays in recurrent BV after oral metronidazole therapy. METHODS Women with abnormal vaginal discharge or odor were enrolled in a cross-sectional study (n=358); the proportion of those infected with Gardnerella vaginalis and A. vaginae was determined by polymerase chain reaction. Women with BV (Nugent score [NS] 7-10 or 4-6 with > or =3 Amsel criteria; n=139) were treated with oral metronidazole (400 mg twice a day for 7 days) and examined at 1, 3, 6, and 12 months or until they reached an NS of 7-10 and recurrence of A. vaginae and G. vaginalis infection was established. RESULTS A. vaginae and G. vaginalis were highly sensitive for BV--96% (95% confidence interval [CI], 91%-98%) and 99% (95% CI, 97%-100%), respectively. However, A. vaginalis was more specific for BV (77% [95% CI, 71%-82%]) than was G. vaginalis (35% [95% CI, 29%-42%]). G. vaginalis was detected in 100% and A. vaginae in 75% of women with recurrent BV; higher organism loads were present in women with recurrent BV. A. vaginae was rarely detected without G. vaginalis, and women in whom both organisms were detected had higher rates of recurrent BV (83%) than women infected with G. vaginalis only (38%) (P<.001). CONCLUSIONS Infection with A. vaginae is more specific for BV than infection with G. vaginalis. The higher recurrence rates in women in whom both A. vaginae and G. vaginalis were detected suggest that A. vaginae makes a significant contribution to BV. However, its etiological role remains unclear.

Persistence of Mycoplasma genitalium Following Azithromycin Therapy

Background To determine clinical outcomes and cure rates for M.genitalium genital infection in men and women following azithromycin 1 g. Methodology Patients attending Melbourne Sexual Health Centre between March 2005 and November 2007 with urethritis/epididymitis, cervicitis/pelvic inflammatory disease and sexual contacts of M.genitalium were tested for M.genitalium by polymerase chain reaction (PCR). M.genitalium-infection was treated with 1 g of azithromycin and a test-of-cure (toc) was performed one month post-azithromycin. Response to azithromycin, and response to moxifloxacin (400 mg daily for 10 days) in individuals with persistent infection post-azithromycin, was determined. Principal Findings Of 1538 males and 313 females tested, 161 males (11%) and 30 females (10%) were infected with M.genitalium. A toc was available on 131 (69%) infected individuals (median = 36 days [range 12-373]). Of 120 individuals prescribed azithromycin only pre-toc, M.genitalium was eradicated in 101 (84%, 95% confidence intervals [CI]: 77–90%) and persisted in 19 (16%, 95% CI: 10–23%). Eleven individuals with persistent infection (9%, 95% CI: 5–15%) had no risk of reinfection from untreated-partners, while eight (7%, 95% CI: 3–12%) may have been at risk of reinfection from doxycycline-treated or untreated-partners. Moxifloxacin was effective in eradicating persistent infection in all cases not responding to azithromycin. Patients with persistent-M.genitalium were more likely to experience persistent symptoms (91%), compared to patients in whom M.genitalium was eradicated (17%), p<0.0001. Conclusion Use of azithromycin 1 g in M.genitalium-infected patients was associated with unacceptable rates of persistent infection, which was eradicated with moxifloxacin. These findings highlight the importance of follow-up in M.genitalium-infected patients prescribed azithromycin, and the need to monitor for the development of resistance. Research to determine optimal first and second-line therapeutic agents for M.genitalium is needed.

Higher-risk behavioral practices associated with bacterial vaginosis compared with vaginal candidiasis

Objective: Bacterial vaginosis has been associated with hormonal factors and sexual practices; however, the cause is unclear, and the notion that bacterial vaginosis is a sexually transmitted infection is still debated. To investigate whether bacterial vaginosis is associated with specific sexual practices or instead has features in common with a sexually transmitted infection, we compared behavioral associations in women with bacterial vaginosis to women with vaginal candidiasis. Methods: Women with symptoms of abnormal vaginal discharge or odor who attended Melbourne Sexual Health Centre between July 2003 and August 2004 were eligible for enrollment in the study. Information on demographics and behavioral and contraceptive practices were collected by self-completed questionnaire. Participants were tested for bacterial vaginosis, Candida spp (microscopy and culture), and sexually transmitted infections. Statistical comparisons were made between women with and without bacterial vaginosis and women with and without candidiasis, using univariate and multivariate analysis. Results: A total of 342 women were enrolled in the study; 157 were diagnosed with bacterial vaginosis, 51 had candidiasis by microscopy, and 95 had candidiasis by culture. Bacterial vaginosis was associated with indicators of high-risk sexual behavior such as a new sexual partner and greater number of male partners in the last year, increased number of lifetime sexual partners, less than 13 years of education, a past history of pregnancy, and smoking (P < .05). Candidiasis was not associated with these risk behaviors and was instead related to practices such as receptive anal and oral sex and douching. Conclusion: The association between bacterial vaginosis and practices that are associated with sexually transmitted infections, in contrast to those observed with candidiasis, suggests a possible sexually transmitted cause. Level of Evidence: II-2