bluuebunny/crossref_metadata_2025 huggingface dataset:
O02.1 A Randomised, Controlled Study to Assess the Efficacy and Safety of Nifuratel Vaginal Tablets on Bacterial Vaginosis
Authors: Mendling W , Caserini M , Palmieri R
Published: July 2013

Background

Bacterial vaginosis (BV) is a polymicrobial infection and the most common cause of vaginal discharge in women during their reproductive years. A randomised, evaluator-blinded, parallel group pivotal study was carried out to assess the efficacy and safety of the local treatment with nifuratel vaginal tablets in comparison with metronidazole vaginal suppositories in premenopausal, non-pregnant women suffering from BV.

Methods

A total of 727 adult women in 38 German sites, with BV diagnosed by Amsel and Nugent criteria, were enrolled after providing their written informed consent. Patients received one course of vaginal treatment with metronidazole 100 mg once daily (o.d.) for six days or nifuratel 250 mg o.d. for ten days. The test of cure visit was performed on day 24 ± 3 after the beginning of the treatment. The efficacy was evaluated using the therapeutic cure rate defined as a combined endpoint including Amsel criteria, clinical signs and symptoms and Nugent score evaluated by a blinded central assessor. The non-inferiority of nifuratel compared to metronidazole at the pre-specified margin of Δ-15% was defined as the clinically acceptable difference between the two active treatments.

Results

The therapeutic cure rate was achieved in the per protocol data set by the 53.7% of women: 54.5% in the nifuratel group and 52.9% in metronidazole treated patients (p = 0.0002). Concerning Nugent score (0–3), the two treatments had similar responder rates: 66.2% nifuratel vs. 66.8% metronidazole (p = 0.0006), same results were obtained in terms of Amsel criteria normalisation 78.9% nifuratel vs. 78.6% metronidazole (p = 0.0001). Nifuratel was slightly better to metronidazole curing vulvovaginal signs and symptoms: 81.2% vs. 78.6% (p < 0.0001).

Conclusion

The study results suggest that nifuratel 250 mg vaginal tablet o.d. for 10 days may be recommended as first-line treatment in BV as well as the golden standard metronidazole since their efficacy is comparable.
O02.2 Susceptiblity of Bacterial Vaginosis (BV)-Associated Bacteria and Lactobacilli to Rifaximin, Metronidazole and Clindamycin
Authors: Hillier S L , Cosentino L , Petrina M , Rabe L
Published: July 2013

Objective

Rifaximin is a semisynthetic rifamycin with poor oral bioavailability, used as an oral agent for the treatment of traveller’s diarrhoea and hepatic encephalopathy. Rifaximin is in development as a topical agent for the treatment of bacterial vaginosis (BV). The objective of this study was to evaluate the antimicrobial susceptibility of vaginal isolates of facultative and anaerobic bacteria to rifaximin, clindamycin and metronidazole.

Methods

A total of 411 unique BV-related bacteria and 100 isolates of lactobacilli recovered from the human vagina of US women during the years 2009–2012 were tested for antimicrobial susceptibility by the agar dilution CLSI reference method to calculate MICs.

Results

Overall, 142 (35%) of the BV-associated vaginal isolates tested were resistant to metronidazole, 63 (15%) were resistant to clindamycin and 11 (2.6%) were resistant to rifaximin. Metronidazole resistance was observed most frequently amongGardnerella vaginalis(n = 100 isolates, 69% resistant),Atopobium vaginae(n = 62, 87% resistant) andMobiluncus(n = 40, 42% resistant), whereas most were susceptible to both clindamycin (197/202; 98% susceptible) and rifaximin (191/202; 95% susceptible). Both rifaximin and metronidazole were effective against all strains ofPrevotella bivia(n = 34),P timonensis(n = 33),Anaerococcus tetradius(n = 21), Finegoldia magna(n = 20) andPeptoniphilus lacrimalis(n = 20), whereas clindamycin resistance was detected among 74%, 42%, 19%, 30% and 30% of these anaerobes isolates, respectively. More than 90% ofPrevotella amnii(n = 33),Peptoniphilus harei(n = 23) andMegasphaera-like bacteria (n = 25) were susceptible to all three antibiotics. As expected, none of theLactobacillusisolates were susceptible to metronidazole, whereas a majority were susceptible to both clindamycin and rifaximinin vitro.

Conclusion

Rifaximin had MIC values for a range of microorganisms associated with BV which were superior or similar to the other two drugs approved for the treatment of this condition and deserves clinical evaluation as a new therapeutic agent for the treatment of BV.
O02.4 Persistent/Recurrent Chlamydial Infection Among STD Clinic Patients Treated with CDC-Recommended Therapies
Authors: Khosropour C M , Duan R , Metsch L R , Feaster D J , Golden M R
Published: July 2013

Background

CDC guidelines recommend azithromycin or doxycycline as treatments for chlamydial infection. Recently, one randomised trial comparing these therapies suggested doxycycline was superior, while another found the two therapies were equivalent. We examined the risk of persistent/recurrent chlamydial infection among patients treated with doxycycline or azithromycin.

Methods

We performed a secondary analysis of data from Project Aware, a randomised, controlled trial of a behavioural intervention. The trial enrolled patients aged ≥ 18 years without a prior HIV diagnosis in 9 U.S. STD clinics in 2010. At baseline, women with urogenital chlamydial infection and men with urethral and/or rectal chlamydial infections were treated with azithromycin or doxycycline, per clinic standard of care. Patients with a positive chlamydia test at 6-month follow-up were considered to have persistent/recurrent infection.

Results

Of 5012 participants, 492 (9.8%) tested positive forC. trachomatisat baseline. Of these, 338 (69%) were treated with doxycycline or azithromycin without a second drug active againstC. trachomatis; 92% (76 of 83) and 88% (225 of 255), respectively, were re-tested at 6 months. Comparing doxycycline and azithromycin, overall 7 (9.2%) and 26 (11.6%), respectively, had persistent/recurrent infection (RR = 0.80, 95% CI = 0.36–1.76). Among persons with urogenital infections, 6 (10.0%) of 60 and 18 (10.1%) of 179 (RR = 0.99, 95% CI = 0 0.41–2.39), respectively had persistent/recurrent infection. Among men with rectal infections, 2 (9.5%) of 21 and 8 (16.3%) of 49 who received doxycycline and azithromycin, respectively, had persistent/recurrent infection (RR = 0.58, 95% CI = 0.14–2.52). On multivariate analysis, persistent/recurrent infection was significantly associated with black (vs. white) race (aRR = 4.29, 95% CI = 1.14–16.16) and rectal (vs. urogenital) infection (aRR = 5.42, 95% CI = 0.99–29.55), but not treatment regimen.

Conclusion

There were no differences in persistent/recurrent urogenital chlamydia infections at six months by treatment type. Treatment failure of rectal infections among men may be more common with azithromycin and merits additional study.
O03.1 Risk Factors For Antimicrobial ResistantNeisseria Gonorrhoeaein Europe
Authors: Cole M J , Spiteri G , Town K , Unemo M , Hoffmann S , Laar M van de , Ison C
Published: July 2013

Introduction

The European Centre for Disease Prevention and Control is responsible for the enhanced surveillance of sexually transmitted infections and co-ordinates the European gonococcal antimicrobial surveillance programme (Euro-GASP) in the European Union and the European Economic Area. Linked patient and antimicrobial susceptibility data from Euro-GASP allows those at risk of acquiring antimicrobial resistantNeisseria gonorrhoeaeto be identified.

Methods

Seventeen countries in 2009 and 21 countries in 2010 and 2011 submitted gonococcal isolates to Euro-GASP, which were tested by Etest or agar dilution for cefixime, ceftriaxone, ciprofloxacin, azithromycin, spectinomycin and gentamicin. Additional patient data linked to the gonococcal isolates susceptibility profiles was collected. All three years antimicrobial susceptibility data and linked patient data were combined. Patient variables associated with resistance were established using a univariate and multivariable analyses of odds ratios. Geometric means for ceftriaxone and cefixime MICs were calculated.

Results

A total of 5034 gonococcal isolates were tested in Euro-GASP from 2009 to 2011. In the multivariable analysis heterosexuals (males only for ciprofloxacin), older patients and those without a concurrent chlamydia infection remained significantly more likely to be infected with isolates displaying cefixime decreased susceptibility and ciprofloxacin resistance. The geometric mean of cefixime and ceftriaxone MICs decreased from 2009 to 2011, most significantly for MSM; MSM had lower geometric means than heterosexuals in 2011. A bimodal MIC distribution of a ‘more susceptible’ and ‘less susceptible’ gonococcal population appears to be emerging alongside this geometric mean decrease.

Conclusion

This Euro-GASP data suggests that the burden of gonococcal antimicrobial resistance is more prevalent among heterosexuals and decreasing in MSM. This study shows the importance of collecting and analysing patient data along with susceptibility data, however improved data numbers and representativeness is required before any focused treatments or public health intervention strategies are initiated.

Abstract O03.1 Table 1

Patient risk factors for antimicrobial resistance (OR, 95% CI from multivariable analysis)

Cefixime decreased susceptibilityCiprofloxacin resistanceMSM11Male heterosexuals2.39 (1.58–3.61)*1.49 (1.21–1.83)*Female2.75 (1.68–4.5)*1.04 (0.8–1.34)< 25 years11≥ 25 years2.07 (1.36–3.13)*1.67 (1.37–2.05)*Chlamydia - yes11Chlamydia - no1.87(1.1–3.16)*2.2 (1.74–2.8)**

P value < 0.05 (from the Pearson Chi2-test)
O03.3 Maximising the Efficiency of Gonorrhoea Treatment by Targeting the Use of Previous First Line Therapies to Susceptible Patients
Authors: Town K , Obi C , Chisholm S , Hughes G , Ison C A
Published: July 2013

Background

Gonorrhoea treatment guidelines change when less than 95% of the infected population is successfully treated with the recommended antimicrobial. Isolates with decreased susceptibility to ceftriaxone, the current recommended therapy, have been identified and if treatment failure becomes problematic there are no new antimicrobials approved. However,Neisseria gonorrhoeaeremains susceptible to penicillin, ciprofloxacin and cefixime in at least two thirds of patients (82%, 68%, and 98% respectively) so it may be possible to target previously recommended antimicrobials to specific population sub-groups.

Methods

Descriptive data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) were analysed for trends in penicillin, ciprofloxacin and cefixime susceptibility across patient sub-groups. Patient characteristics associated with antimicrobial susceptibility were identified using univariate and multivariable analyses. All analyses were performed separately for heterosexuals and men who have sex with men (MSM).

Results

Heterosexual patients whose infection was susceptible to penicillin, ciprofloxacin or cefixime were of black ethnicity, penicillin: 94%, adjusted odds ratio (OR) 3.52 (95% confidence interval (CI) 2.62–4.72), ciprofloxacin: 92%, OR 5.35 (CI 4.08–7.0), cefixime: 99%, OR 3.62 (CI 1.91–6.84), or with concurrent chlamydia infection (penicillin: 94%, 2.34, 1.75–3.13, ciprofloxacin: 92%, 3.37, 2.59–4.38, cefixime: 99%, 2.32, 1.23–4.39). Additionally isolates susceptible to penicillin were found in patients aged 13–24 years (92%, 3.54, 2.63–4.77) or without symptoms (92%, 1.75, 1.28–2.4). All isolates from heterosexuals were fully susceptible to cefixime. In all sub-groups of the MSM population the proportion of isolates susceptible to penicillin, ciprofloxacin or cefixime was below 90%.

Conclusion

The efficiency of gonorrhoea treatment could be maximised by targeting the use of previous first line therapies to specific heterosexual population sub-groups if the treatment threshold is reduced to 90%. Treatment of any MSM with penicillin, ciprofloxacin or cefixime would not be appropriate, as the proportion susceptible to these antimicrobials is much less than for the heterosexual population.
O03.4 Genomic Epidemiology of Neisseria Gonorrhoeae with Reduced Susceptibility to Cefixime in the United States
Authors: Grad Y H , Kirkcaldy R , Trees D , Dordel J , Goldstein E , Weinstock H , Parkhill J , Hanage W P , Bentley S , Lipsitch M
Published: July 2013

Background

Genome sequencing of pathogens has yielded insights into transmission networks and the spread of antibiotic resistance. Here, we report a large-scale genomic epidemiology study ofNeisseria gonorrhoeaeto investigate the emergence and spread of isolates with reduced susceptibility to cephalosporins.

Methods

We sequenced the genomes of 242 gonococcal isolates collected by CDC’s Gonococcal Isolate Surveillance Program (GISP). These isolates comprise all 141 isolates from GISP in 2009–10 with reduced susceptibility to cefixime (cefRS; cefixime MICs ≥ 0.25 µg/ml) and 141 susceptible isolates matched by location, collection date, and sexual orientation of the infected individual. We assessed diversity and association of genes known to contribute to antibiotic resistance, correlated location and phylogenetic clustering to determine sexual networks, and characterised the extent of recombination.

Results

Phylogenetic analysis of single nucleotide polymorphisms (SNPs) within the core genome (34959 SNPs) demonstrates that most cefRSisolates in the US fall into two distinct lineages. We identify several independent acquisitions of a mosaicpenAallele, including evidence of a partial mosaic in an isolate with cefRSand of reversion to an allele conferring cephalosporin susceptibility. Correlating the phylogeny with sexual orientation and geographic location provides evidence for clones circulating in sexual networks, some of which appear geographically restricted and others widespread. Analysis of predicted recombinant regions shows evidence of exchange with otherNeisseriaspp., consistent with prior observations of interspecies mosaicism.

Conclusions

CefRSisolates in the US predominantly derive from two lineages that share the same mosaicpenAsequence, and reflect sexual networks at local and regional scales. Additionally, we quantify the extent of recombination and the correlation of selected alleles with resistance phenotypes. Genomic methods offer detailed insights into the spread of resistant infections, with potential for enhanced surveillance and improved diagnostics.
O03.5 Recent Increases in Gonorrhoea in Europe
Authors: Spiteri G , Haar K , Sfetcu O , Laar M van de
Published: July 2013

Background

Recent reports have described increasing trends of gonorrhoea among men who have sex with men (MSM) in the United Kingdom and women in Sweden. European Union (EU/EEA) surveillance data has also shown increasing rates of gonorrhoea since 2008. We analysed surveillance data to identify the contributions of key populations to this increase.

Methods

Surveillance of gonorrhoea in the EU/EEA is co-ordinated by the European Centre for Disease Prevention and Control (ECDC). Data reported to ECDC in 2008 and 2011 were compared, focusing on countries with an increasing number of gonorrhoea cases, to analyse changes among key populations.

Results

In 2011, 39 179 cases of gonorrhoea were reported from 28 EU/EEA countries. Of these countries, 21 reported a median increase in the number of reported cases of 31% (interquartile range: 22–79%). Among countries reporting increasing cases, 15–24 year olds accounted for 43% of reports in 2011; males accounted for 72%; MSM for 40%. Among MSM, the largest proportion of cases was reported among 25–34 year olds (42%).

Between 2008 and 2011, the number of reported cases increased by 37%. Increases were observed among all age-groups, particularly among 25–34 year olds (61%) and those aged 45+ (78%). Reported cases increased by 51% among males compared to 30% among females. Transmission among MSM increased by 124% since 2008 and, among MSM, the largest increase in reported cases was among those aged 45+ (192%) and 25–34 year olds (173%).

Conclusions

Although reported cases of gonorrhoea increased among all age-groups and both genders between 2008 and 2011, the highest increase occurred among MSM above 25 years of age. Increasing trends may be due to increased awareness and testing, and improved reporting; increased transmission, however, is also likely. Prevention messages targeting these groups need to be reinforced.
O03.6 Using Molecular Typing to Investigate N. Gonorrhoeae Strain Turnover: A Comparative Study of GISP Isolates Collected from Baltimore and San Francisco
Authors: Espinosa K , Gerrity J , Pandori M , Marsiglia V , Hardick J , Barnes M , Hess D , Gaydos C
Published: July 2013

Background

One internationally accepted method for the molecular epidemiologic typing ofNeisseria gonorrhoeaeisNeisseria gonorrhoeaeMulti Antigen Sequence Typing (NG-MAST). NG-MAST utilises DNA sequencing of two variable regions of theN. gonorrhoeaegenome to classify gonococcal isolates into strain types.

Method

We assessed the genetic diversity ofN. gonorrhoeaeisolates in Baltimore (N = 277) spanning the years 2009–2011 compared to San Francisco (N = 539) from 2005–2011, using NG-MAST. All isolates in this project were obtained from the CDC Gonococcal Isolate Surveillance Project (GISP). San Francisco strains were mostly from MSM, while the Baltimore isolates were mostly from a heterosexual population.

Results

NG-MAST results from isolates across that time period revealed a surprising degree of sequence type turnover within the Baltimore area. When compared to the data from San Francisco, theN. gonorrhoeaegenetic diversity trends revealed minimal overlap in sequence families between the two metropolitan areas; SF8238, SF210, and SF 2992 were present in both populations. However, a pair-wise comparison of other strain families revealed two relatively distinct populations; the most prevalent strain families in San Francisco were SF437, SF23, SF3935, and SF1407, while those in Baltimore were SF8234, SF8240, SF865, and SF8262.

Conclusion

These data may imply that the traditional understanding of a gonococcal transmission pattern from west to east cannot accurately depict the strain flow ofN. gonorrhoeaeisolates within these populations. Our data revealed a large amount of strain turnover in both metropolitan areas by year. This raises questions about the entry and transmission ofN. gonorrhoeaewithin the U.S., and the implications of this turnover in regards to the evolution of this organism.
O04.1 The Influence of Hormonal Contraception and Pregnancy on the Vaginal Microbiome, Sexually Transmitted Infections, and Cytokine Responses in a Cohort of Rwandan Sex Workers
Authors: Verwijs M C , Borgdorff H , Wit F W N M , Schuren F H , Lutter R , Verhelst R , Bonten M J M , Wijgert J H H M van de
Published: July 2013

Background

The effects of hormonal contraception and pregnancy on the vaginal microbiome (by molecular methods), acquisition and persistence of sexually transmitted infections (STIs), and genitourinary mucosal immunology are still largely unknown.

Methods

HIV-negative, non-pregnant female sex workers (n = 397) in Kigali, Rwanda, were followed for two years. Demographic, behavioural, clinical, STI and pregnancy data were collected at regular intervals. The vaginal microbiome was cross-sectionally determined using a phylogenetic microarray (n = 174). Women with STIs were purposefully oversampled in this subsample. Inflammatory cytokines were measured in cervicovaginal fluid using Luminex and ELISA methodology (n = 343). Hormonal exposure was defined as use of hormonal contraception (oral or injectable) or a positive urine pregnancy test. Women in the exposure groups were compared to non-pregnant women who did not use hormonal contraception. Adjustments were made for demographic data and sexual risk taking.

Results

At baseline, 12% of the women used hormonal injectables, and 6% oral contraceptives (OC); 7.7% was pregnant. OC use was associated with higher HPV prevalence (aOR 3.09; 95% CI 1.42–7.72), higherChlamydia trachomatisincidence (aOR 7.13; 95% CI 1.40–36.30), and lower syphilis prevalence (0% vs 7.2% in controls) and incidence (0% vs 1.2%). Hormonal injectables were associated with higher HSV-2 prevalence (aOR 2.08; 95% CI 1.23–3.50). Pregnancy was weakly associated with higherTrichomonas vaginalis(aOR 1.67; 95% CI 0.97–2.88) and vaginal yeast (aOR 1.95; 95% CI 0.99–3.82) incidence. Six vaginal microbiome clusters were identified. No associations between hormonal exposure status and vaginal microbiome clusters were found; however, pregnant women had lowerGardnerella vaginalislevels. Pregnant women had higher IL-8 levels in cervicovaginal fluids than non-exposed women.

Conclusions

Both hormonal contraception and pregnancy were associated with higher STI incidence. Overall, vaginal inflammation and microbiome composition were similar among groups, but pregnant women had lowerGardnerellaand higher IL-8 levels.
O04.2 Hormonal Contraception is Associated with a Reduced Risk of Bacterial Vaginosis: A Systematic Review and Meta-Analysis
Authors: Vodstrcil L A , Hocking J S , Law M , Walker S , Fairley C K , Tabrizi S , Bradshaw C S
Published: July 2013

Background

We conducted a systematic review and meta-analysis of published data to examine the association between hormonal contraception (HC) and bacterial vaginosis (BV).

Methods

Three databases (Medline, Web of Science and Embase) were searched until the end of January 2013 and duplicate references removed. Inclusion criteria were (1) > 20 BV cases; (2) data available to derive the association between HC and BV; (3) > 10% of participants used HC; (4) accepted BV diagnostic method. Data extracted included: type of HC, BV diagnostic method, and BV outcome (prevalent, incident, recurrent). Meta-analyses were conducted to calculate overall and pooled odds/risk ratios (OR/RR), stratified by HC-type and BV outcome. This systematic review is registered with PROSPERO (CRD42013003699).

Results

Of 1710 unique references identified, 328 were assessed for eligibility and 48 studies met inclusion criteria. Overall, 36 reported BV-prevalence, 12 BV-incidence and 3 BV-recurrence. Twenty three studies reported data for combined-HC, 9 for progesterone-only HC and 23 did not specify HC-type. Diagnostic methods included: Nugent’s (n = 31), Amsel’s (n = 15), Spiegel’s (n = 1) and Ison-Hay (n = 1). Pooled BV prevalence was 30.7% (95% CI: 26.7–34.7%) and ranged from 4.7%–66.7%, with > 99% of the observed variance of prevalent BV explained by heterogeneity (I2 = 99.6%). The pooled effect of any HC-use on the composite-BV outcome (prevalent/incident/recurrent) was OR = 0.67 (95% CI: 0.62–0.71). When stratified by BV outcome, any HC-use was associated with decreased risk of prevalent (OR = 0.63; 0.58–0.68), incident (RR = 0.78; 0.68–0.87) and recurrent (RR = 0.61; 0.49–0.73) BV. When prevalent BV was stratified by HC-type, combined-HC (OR = 0.68; 0.62–0.74), unspecified HC-type (OR = 0.60; 0.53–0.67), and progesterone-only methods (OR = 0.67; 0.46–0.88) were all associated with decreased risk of prevalent BV.

Conclusion

HC-use is associated with a significant and consistent decreased risk of all BV outcomes, with a greater reduction in risk for prevalent than incident BV. Surprisingly, both combined and progesterone-only contraceptive methods were associated with reduced risk of prevalent BV.
O04.3 Correlates of IncidentTrichomonas VaginalisInfections Among African-American Adolescent Females
Authors: Swartzendruber A , DiClemente R J , Sales J M , Brown J L , Rose E S
Published: July 2013

Background

Trichomonas vaginalisis associated with adverse reproductive health outcomes, including HIV. Despite marked racial disparities, few studies have reported factors related to incidentT. vaginalisinfection exclusively among young African-American women. The objective was to identify correlates of incidentT. vaginalisinfections among African-American adolescent females.

Methods

Data were collected via audio computer self-interviews at baseline and every 6 months for 18 months from 701 African-American females (14–20 years) enrolled in an HIV prevention trial. Vaginal swabs were self-collected at each assessment and assayed forT. vaginalis,Chlamydia trachomatisandNeisseria gonorrhoeaeusing DNA amplification. Generalized estimating equations assessed associations between incidentT. vaginalisinfection,defined as a positive test result subsequent to a negative result or documented treatment, and sociodemographic characteristics, partner-level factors, HIV/STI-associated behaviours and STIs. Factors significant at p < 0.1 in bivariate analyses were entered into a multivariable model, adjusting for age and trial condition. The final model was obtained using backward selection procedures.

Results

Of 606 (86.4%) participants who completed ≥ 1 follow-up assessment, an incidentT. vaginalisinfection was detected among 20.0% (n = 121). Trial condition was not independently associated with incident infection (p = 0.21). Significant correlates included: receipt of an increasing number of forms of government assistance (AOR: 1.20, 95% CI: 1.01, 1.42), cigarette smoking (AOR: 1.70, 95% CI: 1.08, 2.67), smoking marijuana an increasing number of days in the past 3 months (AOR: 1.02, 95% CI: 1.00, 1.04), concurrentC. trachomatis(AOR: 2.28, 95% CI: 1.43, 3.66) andN. gonorrhoeae(AOR: 5.99, 95% CI: 3.10, 11.57) infection and testing positive forT. vaginalisat the previous assessment (AOR: 4.56, 95% CI: 2.99, 6.96).

Conclusions

IncidentT. vaginalisinfections were common. Strategies to reduce infection rates among this population may include improving partner notification and treatment services and addressing the role of substance use on sexual risk.
O04.4 Seroprevalence of Herpes Simplex Virus Types 1 and 2 United States, 1999–2010
Authors: Bradley H , Markowitz L E , Gibson T , McQuillan G M
Published: July 2013

Background

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are common infections with serious sequelae. HSV-1 is an increasingly important cause of genital herpes in industrialised countries, potentially due to less acquisition of HSV-1 during childhood or to changes in sexual behaviour.

Methods

Using nationally representative data from the National Health and Nutrition Examination Surveys (NHANES), we examined change in seroprevalence of HSV-1 and HSV-2 among 14–49 year olds in the United States. We compared seroprevalence in 1999–2004 with 2005–2010, and examined seroprevalence among 14–19 and 20–29 year-olds stratified by socio-demographic characteristics and sexual behaviours. We also reviewed HSV-1 and HSV-2 seroprevalence from 1976–1980 to 2005–2010.

Results

In 2005–2010, the seroprevalence of HSV-1 was 53.9%, and the seroprevalence of HSV-2 was 15.7%. From 1999–2004 to 2005–2010, HSV-1 seroprevalence declined by nearly 7% (P < 0.01), but HSV-2 seroprevalence did not change significantly. The largest decline in HSV-1 seroprevalence from 1999–2004 to 2005–2010 was observed among 14–19 year olds, among whom seroprevalence declined by nearly 23%, from 39.0% to 30.1% (P < 0.01). In this age group, HSV-1 seroprevalence declined among young men and women, non-Hispanic blacks and whites, and those living above and below the federal poverty level. Overall, HSV-1 seroprevalence declined more than 10% from 60.1% in 1976–1980 to 53.9% in 2005–2010 (P < 0.01). Among 14–19 year olds, HSV-1 seroprevalence declined more than 29%, from 42.6% to 30.1% (P < 0.01). Overall, HSV-2 seroprevalence increased slightly from 13.4% in 1976–1980 to 15.7% in 2005–2010 (P = 0.02).

Conclusions

An increasing number of adolescents lack HSV-1 antibodies at sexual debut and are susceptible to genital HSV-1 infection. In the absence of declines in HSV-2 infections, the prevalence of genital herpes may increase.
O04.5 Comparison of the Clinical and Demographic Characteristics of Neonatal Herpes Infections Caused by Herpes Simplex Virus Type 1 and Type 2; Findings from a Population-Based Surveillance System, 2006–2012
Authors: Schillinger J A , Washburn K , Klingler E , Blank S , Pathela P
Published: July 2013

Background

The epidemiology of neonatal herpes infection (nHSV) is changing as herpes simplex virus type 1 (HSV-1) is an increasingly common cause of genital herpes. Few sources of population-based data for nHSV exist; nHSV has been a notifiable disease in New York City (NYC) since 2006.

Methods

To compare the clinical and demographic characteristics of nHSV due to HSV-1 and herpes simplex virus type 2 (HSV-2), we used standard case investigation forms to abstract infant inpatient/outpatient medical records, and maternal labour and delivery records for babies ≤ 60 days of age diagnosed with laboratory-confirmed herpes infection and reported in NYC during 2006–2012. Disease syndromes were grouped as invasive (disseminated/central nervous system infection/death) versus localised (skin/eye/mucous membrane infection,). Cases lacking liver function test results, or lumbar puncture were excluded from analyses of disease syndrome. Bivariate analyses compared clinical and demographic characteristics by viral type.

Results

There were 91 cases reported (HSV-1, 40; HSV-2, 36; untyped, 15). Among 76 cases with viral typing, the majority (53%; 40/76) were HSV-1. There were no statistically significant differences by viral type for any variables examined: age ≤ 7 days at presentation (HSV-1, 59% versus HSV-2, 41%), fever (HSV-1, 38% versus HSV-2, 46%), vesicles (HSV-1, 46% versus HSV-2, 53%), invasive disease (HSV-1, 53% versus HSV-2, 70%), case fatality rate (HSV-1, 18% versus HSV-2, 19%), maternal history of genital herpes (HSV-1, 20% versus HSV-2, 20%), maternal genital lesions at delivery (HSV-1, 8% versus HSV-2, 3%), vaginal delivery (HSV-1, 69% versus HSV-2, 61%), white non-Hispanic maternal race/ethnicity (HSV-1, 26% versus HSV-2, 12%), maternal age < 20 (HSV-1, 15% versus HSV-2, 27%).

Conclusions

Neonatal herpes infections due to HSV-1 and HSV-2 have a similar presentation, and death rate. To prevent nHSV, candidate HSV vaccines will need to protect against HSV-1, as well as HSV-2 infection in women.
O04.6 Mycoplasma Genitalium- Is It a Pathogen in Acute Pelvic Inflammatory Disease (PID)?
Authors: Wiesenfeld H C , Hillier S L , Meyn L , Trucco G , Amortegui A , Macio I S , Rabe L , Cosentino L , Darville T
Published: July 2013

Background

PID is a polymicrobial infectious condition of the female upper genital tract.Neisseria gonorrhoeae(GC) andChlamydia trachomatis(CT), long considered the predominant organisms involved in the pathogenesis of PID, are identified in fewer than half of U.S women diagnosed with acute PID.Mycoplasma genitalium(MG) is associated with male urethritis and some evidence suggests an association with other STD syndromes including cervicitis and PID. Our objective was to examine the association between MG and acute PID.

Methods

The ACE Trial is a randomised double-blind study evaluating the value of anaerobic therapy for acute PID. At enrollment, specimens were collected from the cervix and endometrium for testing for GC, CT and MG by transcription-mediated amplification. Histology was performed on endometrial tissue. Identification of cervical and endometrial organisms was correlated with endometritis.

Results

Among the 125 women diagnosed with acute PID, twenty two percent (n = 27) tested positive forM. genitalium, while CT, GC and bacterial vaginosis were present in 14%, 7% and 54%, respectively. Forty six women (37%) had histologic endometritis. Histologic endometritis was more common among those having cervical infections with GC, CT or MG than uninfected women (66% vs. 24%, p < 0.001). Among women with endometritis, GC, CT and MG were present in 17%, 30% and 36%, respectively. Endometritis was present in 71% (20/28) of women with endometrial GC, CT or MG. Endometrial identification of GC (100% vs. 34%, p < 0.05), CT (77% vs. 32%, p < 0.01) and MG (64% vs. 33%, p < 0.05) were each independently associated with endometritis.

Conclusion

Mycoplasma genitaliumis identified in 22% of women diagnosed with acute PID. Similar to CT and GC,the presence of MG in the endometrium is highly associated with endometritis among women diagnosed with PID. This study suggests thatM. genitaliummay play an important role in the pathogenesis of PID.
O05.2 Measuring Syphilis: Quantitative PCR Can Be Used to Monitor Treatment Response
Authors: Tipple C , Hodson L , Jones R , Rayment M , Nwokolo N , McClure M , Taylor G
Published: July 2013

Background

The humoral response toTreponema pallidum(T. pallidum), which causes syphilis, is divided into ‘non-specific’ anti-lipid and specific anti-treponemal protein antibodies. A four-fold reduction in anti-lipid antibodies is used to diagnose cure, which can take six or more months.

Quantitative PCR (qPCR) can measureT. pallidumDNA copies in blood and ulcer samples. Bacteraemia is more common and of higher load in early disease.

We present a pilot study monitoring the early treatment response in patients with infectious syphilis by qPCR.

Methods

Patients with symptomatic primary or secondary disease were admitted to hospital and following baseline sampling were treated with 2.4 M units of benzathine penicillin. Whole blood was collected into EDTA and Tempus RNA preservation tubes and the ulcer sampled using a philtre paper strip every four hours forT. pallidumDNA (tpp047gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Standard serological follow-up was performed.

Results

Three men were recruited (two secondary, one primary). All were homosexual and two were HIV-1 infected.

Blood DNA quantification and clearance: A mean peak-level of 1611(range 1212)tpp047copies/ml was detected and mean half-life for clearance (t½ clearance) was 7.89 hours (range 5.34). Blood RNA: Mean peak-level 8829(range 20366)16SrRNAcopies/ml blood; (t½ clearance) 5.24 hours (range 0.78). Ulcer DNA 1.14 × 105copies/strip and RNA 4.35 × 107copies/strip with a t½ (clearance) of 1.67 and 3.76 hours, respectively.T. pallidumnucleic acids were undetectable in all samples after 56 hours.

All patients had serology consistent with disease stage at baseline and cure at one month.

Conclusions

T. pallidumqPCR presents a novel and quick way of monitoring early syphilis treatment efficacy. Both DNA and RNA may be suitable targets to measure bacterial clearance from blood and ulcer exudates.

Ulcers may be non-infectious as soon as 56 hours post-treatment.
O05.4 Association Between Chlamydia Trachomatis Genital Infection and the Vaginal Microbiome
Authors: Ma B , Brotman R M , Gajer P , Fadrosh D , Mahurkar A , White O , Terplan M , Bavoil P , Forney L J , Ravel J
Published: July 2013

Background

Chlamydia trachomatis(CT) genital infection is one of the most widespread sexually transmitted infections (STIs). It is thought that certain types of vaginal microbiota are better able to prevent STIs, however, very little is known about the relationships between species and genomic composition of the vaginal microbiome and risk of infection. Information about these can be used to advance prevention strategies for STIs. We sought to characterise the vaginal microbiome at the time of diagnosis and after treatment of CT infection.

Methods

101 women with CT genital infection were recruited to a longitudinal study in Baltimore, MD. Participants were treated at diagnosis and returned for clinical visits every 3 months for 9 months, at which times the vaginal microbiota was determined using 16S rRNA analysis. We further applied high-throughput metagenomics to characterise the genomic makeup of the vaginal microbiome.

Results

The average age of participants was 19.3 (range 14–28) and 92% were African-American. During CT infection, comprehensive surveys of the vaginal microbiota demonstrated two distinct community state types characterised by: (1) a complex assemblage of strict anaerobes with low proportions ofLactobacillusspp. (60% of samples) or (2) a high relative abundance ofLactobacillus iners-dominated communities (37% of samples).Metagenomic evaluation suggested unique characteristics of the genomes of the dominant species in these communities (i.e.,L. iners,Gardnerella vaginalis).L. inersappeared more genetically diverse than otherLactobacillusspecies.

Conclusions

Complex communities of strict anaerobes with low proportions ofLactobacillusor specificL. inersgenome types represented a hallmark of the chlamydia-infected state in this population. SomeL. inersmay be better suited to adapt to diverse environments while others may be contributing factors to an at-risk microbiome. In the era of personalised medicine, future work will enhance our ability to intervene and establish a protective vaginal microbiome.
O05.5 A Longitudinal Study of the Vaginal Microbiota and HPV Detection
Authors: Brotman R M , Shardell M D , Gajer P , Tracy J K , Zenilman J M , Ravel J , Gravitt P E
Published: July 2013

Background

The vaginal microbiota can be clustered into six community state types (CSTs): 4 are dominated byLactobacillus iners, L. crispatus, L. gasseri, L. jensenni, and 2 lack significant numbers ofLactobacillusspp. (termed CST IV-A and IV-B). CST IV-A is characterised by a diverse assemblage of strict anaerobes, while CST IV-B has higher proportions of the generaAtopobium, Gardnerella,among others. We sought to describe the relationship between vaginal microbiota and human papillomavirus (HPV) detection.

Methods

Thirty-two reproductive-age women self-collected mid-vaginal swabs twice-weekly for 16 weeks (n = 937 samples). Participants reported behaviours on daily diaries. Vaginal bacterial communities were characterised by pyrosequencing of barcoded 16S rRNA genes (V1-V2 region). Each swab was tested for 37 types of HPV DNA using the Roche HPV Linear Array genotyping test. The effects of CSTs on the rate of transition between HPV-negative and HPV-positive states were assessed using continuous-time Markov models. Additive mixed effects logistic regression and additive mixed effects Poisson models were used to model high risk HPV (hrHPV) and count of HPV types, respectively, with normalised menstrual cycle time.

Results

Participants had an average of 29 (range 25–33) samples tested for HPV, with point prevalence ranging from 58 to 77% and 16-week period prevalence of 84%. CST was significantly associated with changes in HPV status (p < 0.001).L. gasseri-dominated CSTs had the fastest HPV remission rate (HPV-positive to no detection) and CST IV-B had the slowest rate compared toL. crispatus-dominated CSTs (adjusted transition rate ratio (aTRR):7.58, 95% CI: 1.77–32.42 and aTRR:0.31, 95% CI: 0.09–1.05, respectively). Detection of hrHPV and count of different HPV types were highest in the middle of the menstrual cycle.

Conclusion

Vaginal microbiota dominated byL. gasseriwere associated with increased clearance of detectable HPV. A mid-cycle increase in HPV detection suggests a role for sex hormones in modulating latent infection.
O05.6 EndometrialGardnerella VaginalisandAtopobium VagineaAre Associated with Histologic Endometritis Among Women with Clinically Diagnosed Pelvic Inflammatory Disease (PID)
Authors: Hillier S L , Rabe L K , Meyn L , Macio I , Trucco G , Amortegui A , Darville T , Wiesenfeld H C
Published: July 2013

Objective

WhileNeisseria gonorrhoeae(GC) andChlamydia trachomatis(CT) are known to cause PID, many women with clinical signs and symptoms of PID and histologic evidence of endometritis have neither of these pathogens. Our objective was to describe microorganisms in the upper genital tract of women with PID, and to evaluate their association with histologic endometritis.

Methods

Women presenting with symptoms and meeting the CDC diagnosis of PID had an endometrial biopsy obtained by Pipelle, and the tissue was split for microbiological and histological assessment. Cultivated microorganisms were identified using phenotypic and genotypic characteristics. Fisher’s exact tests were used to assess the association between microorganisms and endometritis (plasma cells ± neutrophils).

Results

Of 136 women with clinical PID, 55 (40%) had histologic evidence of endometritis, and endometrial GC and/or CT was associated with endometritis (29% vs. 6%, P < 0.001). In addition to STIs, a broad range of bacteria representing 63 different species were recovered from 53 (39%) of the endometrial biopsy samples, including 8 novel species. The recovery of any non-GC/non-CT organisms from the endometrium was associated with histologic endometritis (53% vs. 30%, P = 0.008). BothG. vaginalis(35% vs. 16%, P = 0.01) andA. vaginae(22% vs. 3%, P < 0.001) were associated with histologic endometritis. Other anaerobic bacteria associated with bacterial vaginosis includingPrevotella timonensis, P. amniiandPeptoniphilus hareiwere also more frequent in the endometrium of women having endometritis (11% vs. 3%, P = 0.06) but this did not reach statistical significance. After excluding women having GC and/or CT,A. vaginaewas still independently associated with endometritis (17% vs. 3%, P = 0.03).

Conclusions

The recovery of non STIs from the endometrium is associated with histologic endometritis among women with clinically diagnosed PID.A. vaginaemay play an etiologic role in PID and merits further evaluation for its role in nongonococcal/nonchlamydial PID.
O06.1 Evaluation of 5 Different Tests For Trichomonas Vaginalis (TV) Infection and Cost Effective Planning For Clinical Implementation
Authors: Nathan B , Appiah J , Heron D , Saunders P , Brum R , Alexander S , Baraitser P , Ison C
Published: July 2013

Background

TV is the most common non-viral STI in the world. Despite this, TV infection in UK Genitourinary clinics is mainly (and often exclusively) diagnosed by wet mount microscopy alone. Microscopy is known to have a low and variable sensitivity and therefore greatly underestimates the true prevalence of TV infection.

Objectives

A clinical trial was conducted to evaluate the performance of five methods for detecting TV: an in-house PCR; the Aptima TV kit; the OSOM Trichomonas Rapid Test (POCT); culture and microscopy to diagnose infection in symptomatic women. The results of the study were used to power a financial model for clinical implementation of a molecular test.

Methods

Symptomatic women were recruited for testing. Results and resource costs from the study were extrapolated to calculate the cost of implementing POCT and in house PCR compared to wet mount microscopy in the clinic.

Results

A composite reference standard of 2 more or more positives was used. 246 women were recruited of which 24 had a positive test by 2 or more of the 5 methods. Aptima TV kit, POCT, Real-time PCR and culture (sensitivities 92, 92, 88 and 88%) all out performed wet-mount microscopy (sensitivity 38%). The prevalence based on two tests as reference standard was 9.75%.

Conclusions

Cost modelling showed although initial outlay costs for PCR and POCT were high, savings were made in labour costs. PCR and POCT would improve the rate of TV diagnosis in this group and therefore reduce repeat visits due to false positive results. PCR requires additional clinical time for recalling the patient for a further visit to give a positive result, treatment and contact tracing. Implementation of newer tests could potentially reduce clinical cost and improve patient outcomes in the long term.
O06.2 A Pilot Randomised Controlled Trial of High-Dose Vitamin D Supplementation to Prevent Recurrence of Bacterial Vaginosis
Authors: Turner A Norris , Reese P Carr , Anderson J , Fields K S , Ervin M , Klebanoff M , Jackson R
Published: July 2013

Background

Bacterial vaginosis (BV) is the most common cause of vaginal infection worldwide and is associated with myriad negative reproductive health outcomes. Several cross-sectional studies indicate that women with low vitamin D levels have increased BV prevalence.

Methods

This randomised, double-blinded, placebo-controlled trial started enrollment in September 2011 and concluded follow-up in January 2013. Women (n = 126) with symptomatic BV were enrolled from an urban STD clinic in the midwestern United States. All participants received standard metronidazole therapy. Intervention participants (n = 63) also received nine doses of 50,000 international units of cholecalciferol (vitamin D3) over 6 months; control arm women (n = 63) received matching placebo. BV status was assessed via Nugent scoring at three follow-up visits over six months. The primary analysis will be intention-to-treat using extended Cox proportional hazard models.

Results

Participants’ median age was 26. Three-quarters (75%) of women were black and 25% were white. All reported a lifetime history of sex with men, and 29% also had a lifetime history of sex with women. At baseline, median serum vitamin D levels (measured as 25-hydroxy vitamin D) were the same for intervention and control women at 15.85 ng/mL (interquartile range (IQR): 12.1–21.4 ng/mL); levels < 20 ng/mL are considered insufficient. Eight-one percent of participants returned for one or more follow-up visits. At trial completion, median vitamin D level among intervention women was 30.5 ng/mL (IQR 24.4–37.7 ng/mL), vs. 17.8 ng/mL among control women (IQR: 11.7–27.1 ng/mL). Nugent scoring is ongoing with primary results available in early spring 2013.

Conclusion

Immunologic mechanisms regulated by vitamin D may play a role in BV recurrence, but no previous study has examined whether supplementing women with vitamin D will impact subsequent development of BV. If effective against BV, vitamin D supplementation can have worldwide impact as a safe, simple intervention.
O06.3 Macrolide Resistance of Mycoplasma Genitalium in France Directly Detected in Clinical Specimens by Real-Time PCR and Melting Curve Analysis
Authors: Touati A , Peuchant O , Skov-Jensen J , Bébéar C , Pereyre S
Published: July 2013

Objectives

Mycoplasma genitalium(MG) is a sexually transmitted organism associated with non-gonococcal urethritis in men and several inflammatory reproductive tract syndromes in women. These infections are commonly treated with azithromycin. However macrolide resistance has been reported and is associated with point mutations in domain V of the 23S rRNA gene. In order to evaluate the prevalence of macrolide resistance in MG in French clinical specimens, we first used a recently published High Resolution Melting (HRM) assay. Because wild-type and mutated MG were hardly discriminated in MG-positive clinical specimens, we developed a new molecular assay for the rapid detection of macrolide resistance.

Methods

Between January 2011 and September 2012, 207 urogenital MG-positive clinical specimens were collected from 185 patients. For the detection of macrolide resistance-associated mutations, we designed a real-time PCR based on fluorescence resonance energy transfer (FRET) coupled with melting curve analysis. The assay was first validated on macrolide-resistant MG isolates with characterised A2058G/C and A2059G mutations (Escherichia colinumbering), then optimised to be applied directly on clinical specimens. Resistant genotypes were confirmed by 23S rRNA gene sequencing.

Results

Among 207 MG-positive clinical specimens, 136 from 119 patients were amplified with our assay, showing a sensitivity of 65.7% (136/207). A substitution in the 23S rRNA gene was found in 14.2% (17/119) of the patients, with a rate of 14.5% in 2011 and 14% in 2012. Nine and eight clinical specimens harboured the A2059G and A2058G mutations, respectively. In four cases, a mixed population of wild-type and mutated MG was observed.

Conclusion

Macrolide resistance prevalence of MG is 14.2% in France. Our FRET PCR assay is able to discriminate wild-type from resistant genotype in one reaction directly in clinical specimen. It will allow clinicians to shorten the time to initiate effective treatment and contribute to reduce transmission of resistant strains.