bluuebunny/crossref_metadata_2025_split huggingface dataset:
S15.1 Frequent Viral Introductions Sustain Local HIV Epidemics in Rural Africa
Authors: Grabowski M K , Lessler J , Redd A , Kagaayi J , Laeyendecker O , Nalugoda F , Serwadda D , Wawer M , Quinn T C , Gray R H 
Published: July 2013

BackgroundIt is often assumed that local sexual networks play a dominant role in HIV spread in sub-Saharan Africa. However, the extent to which continued HIV transmission in rural African communities, home to two-thirds of the continent’s population, is driven by intra-community sexual networks versus viral introductions from outside of communities remains unknown.MethodsWe analysed the spatial dynamics of HIV transmission in rural Rakai District, Uganda using population-based cohort data on 14594 individuals within 46 communities experiencing a generalised HIV epidemic (prevalence 12·%, incidence ∼2 per 100 person years). We applied spatial clustering statistics, phylogenetic analyses, and probabilistic transmission models to quantify the relative contributions of viral introductions versus local HIV transmission, including household transmission, to HIV incidence.ResultsIndividuals in households with incident (n = 189) or prevalent (n = 1597) HIV-infected persons were 3·2 (95% CI: 2·7–3·7) times more likely to be HIV-infected, compared to the population in general, but spatial clustering outside of households was weak and confined to distances < 500m. There was high viral diversity: only 34% of infected persons phylogenetically clustered with at least one other participant. One-third of phylogenetic clusters were individuals sharing a household. Of the remaining two-thirds, 71% crossed community boundaries. We estimate that 39% (95% CI: 32–44%) of viral transmissions occurred within stable household partnerships and that 40% (95% CI: 34–42%) of transmissions were from named extra-household sexual contacts, of which 62% (95% CI: 55–70%) were non-stable partners from outside the community.Interpretation: External HIV introductions into rural communities are common and account for a substantial proportion of new HIV infections in Rakai, Uganda. Our findings suggest that combination HIV prevention will most effectively control local HIV epidemics when implemented at broad spatial scales, and imply a need to identify key populations serving as sources of introduced infections into general populations.
S15.3 Modification of Sexual Networks and Sexual Risk For Men Having Sex with Men (MSM) by the Internet
Authors: Marcus U , Schmidt A J 
Published: July 2013

The Internet provides new opportunities for sexual minorities to communicate and interact. Access to internet may facilitate coming-out for young MSM, sexual identity formation, and community building. On the other side the internet partly substitutes social and sexual venues where MSM congregate. Population and individual level aspects of internet communication among MSM were analysed based on data collected in the European MSM Internet Survey (EMIS).EMIS was a large collaborative project of public health, academia and community based organisations from 35 European countries. The survey was online from June through August 2010, advertised on a large range of MSM websites. The questionnaire anonymously collected data from MSM across Europe. Among others, detailed information on the last sexual intercourse with a non-steady partner was collected.The analysis is based on 174,209 eligible respondents. Participation rates in 38 countries with more than 100 respondents varied considerably (0.3 – 6.8/10,000 inhabitants) and correlated with internet access. A comparison of self-reported new diagnoses of HIV and national surveillance data suggests different relative sizes of MSM populations in different countries. Among men reporting a non-steady sex partner in the last 12 months, 58% had met this partner on the internet. Compared with partners met in venues, serostatus communication with internet partners was more frequent, respondents more often already had sex with their internet partners before, and partners were more often presumed HIV seroconcordant. Contrastingly, refraining from anal sex was less often an option for partners met on the internet.Improved access to internet may increase the relative size of MSM populations by involving a larger number of individuals into sexual networks. With broadening access to internet risk reducing aspects like increased communication before sexual encounters become more pronounced. Promoting protective and preventive behaviours can counter adverse effects of the internet on the HIV epidemic.
S16.3 Recurrent TV: The Potential of Molecular Techniques to Improve Clinical Practise
Authors: Hobbs M M 
Published: July 2013

Infection with the widespread protozoan pathogenTrichomonas vaginalis(TV) does not result in lasting immunity, and recurrent infections are common. Whether due to unrecognised, inadequately treated or repeatedly acquired TV infections, recurrent vaginitis in women, nongonococcal urethritis and chronic prostatitis in men are well-recognised and challenging clinical conditions. Despite increased recognition in the STI research community of the adverse consequences of trichomoniasis in women and men and the potential for TV infection to increase transmission of HIV and other STIs,T. vaginalisinfection remains underappreciated by clinicians, public health professionals, policy makers and patients. Trichomoniasis is not a reportable STI in most countries, and TV infection is often asymptomatic, thus many infections are neither diagnosed nor treated. Symptomatic infection in women is the clinical presentation most likely to be recognised and treated, but treatment of male sexual partners of infected women is infrequent or inadequate, and testing and treatment of trichomoniasis in male patients is rare. Thus, reservoirs of infection persist.Recent improvements in molecular diagnostics for detection of TV in women and men have the potential to improve clinical practise. Rapid antigen detection tests offer point of care testing and improved treatment options in settings where technically complex and costly nucleic acid amplification tests (NAATs) are not available, and NAATs offer highly sensitive and specific testing options for detection of TV in urogenital specimens commonly tested for other sexually transmitted pathogens includingN. gonorrhoeaeandC. trachomatis. With enhanced awareness, availability and application of these molecular tests, better detection and treatment of trichomoniasis in women and in their sexual partners can be achieved with eventual reduction of the adverse reproductive consequences associated withT. vaginalisinfection.
O01.5 Efficacy of RG1-VLP Vaccination Against Genital and Cutaneous Human Papillomavirusesin Vitroandin Vivo
Authors: Schellenbacher C , Kwak K , Fink D , Shafti-Keramat S , Huber B , Jindra C , Roden R , Kirnbauer R 
Published: July 2013

Licensed human papillomavirus (HPV) vaccines, based on virus-like particles (VLP) self-assembled from major capsid protein L1, afford type-restricted protection against types 16/18/6/11 (or 16/18 for the bivalent vaccine), which cause 70% of cervical carcinomas (Cxca) and 90% of genital warts. However, they do not protect against less prevalent high-risk types causing 30% of CxCa, or cutaneous HPV. The minor capsid protein L2 confers low-level immunity to type-common epitopes.Chimeric RG1-VLP presenting HPV16L2 amino acids 17–36 (RG1 epitope) within the DE-surface loop of HPV16L1 induce cross-neutralisationin vitro. We hypothesised, that RG1-VLP vaccination protects against a large spectrum of mucosal and cutaneous HPV infectionsin vivo.L2-specific antibody and CTL responses in RG1-VLP vaccinated rabbits were determined by ELISA and ELISPOT assays. Cross-neutralisation was analysed using native or pseudovirion (PsV) assays. Vaccine efficacyin vivowas determined in a mouse genital challenge model.Immunization with RG1-VLP adjuvanted with human-applicable alum-MPL induced robust L2 antibodies (ELISA titers 2,500–12,500), which cross-neutralised mucosal high-risk HPV26/33/35/39/68/59/68/73/69/53/34, low-risk HPV6/11/32/40/44/70, and cutaneous HPV2/27/3/76 (titers 25–1,000), and a vigorous CTL response.In vivo, mice were efficiently protected against experimental vaginal challenge with mucosal high-risk PsV types HPV16/18/45/31/33/52/58/35/39/51/59/68/56/73/26/53/66/34 and low-risk HPV6/43/44. Enduring protection was demonstrated 1 year after vaccination.RG1-VLP is a promising next-generation vaccine with broad efficacy against all relevant mucosal and also cutaneous HPV types.
O02.3 Treatment Outcomes For Persistent Mycoplasma Genitalium-Associated NGU: Evidence of Moxifloxacin Treatment Failures
Authors: Manhart L E , Khosropour C M , Gillespie C W , Lowens M S , Golden M R , Totten P A 
Published: July 2013

BackgroundRecent treatment trials have demonstrated low efficacy of doxycycline againstMycoplasma genitalium(MG) and increasing resistance to azithromycin. Treatment with azithromycin is recommended for persistent NGU if not used for the initial episode. We evaluated microbiologic cure rates for men with NGU and persistent detection of MG.MethodsEnglish-speaking men aged 16 years attending the STD clinic in Seattle, WA with NGU (urethral discharge or urethral symptoms plus ≥ 5 PMNs/HPF) were enrolled in a randomised trial of NGU therapy between January 2007 and July 2011. Urine was tested for MG by PCR. Men received 1g azithromycin plus placebo doxycycline or doxycycline (100mg bid x 7d) plus placebo azithromycin. Treatment failures after 3 weeks received ‘reverse therapy’ (active doxycycline if they first received active azithromycin and vice versa). Persistent failures after 6 weeks received moxifloxacin (400mg x 7d). After September 2010, microbiologic failures at 3 weeks received moxifloxacin.ResultsOf 606 enrolled men, 65 were positive for MG at enrollment and returned after 3 weeks. Microbiologic failure (positive MG test) occurred in 23/38 (60.5%) who received azithromycin and 19/27 (70.4%) who received doxycycline (p = 0.41). Of the 37 men with microbiologic treatment failure who received ‘reverse therapy’ and returned after 6 weeks, 19 (51.4%) had persistent detection of MG, including 14/20 (70.0%) retreated with doxycycline and 5/17 (29.4%) retreated with azithromycin (p = 0.02). All 19 men were prescribed moxifloxacin; 16 returned at 9 weeks and 2 (12.5%) had microbiologic failure, despite clinical cure. Four men received moxifloxacin after initial failure; 1 had microbiologic failure at 6 weeks, was retreated with moxifloxacin and microbiologically cured at 9 weeks.ConclusionOne half of MG-positive men retreated with a second standard NGU treatment regimen experienced microbiologic treatment failure. Moxifloxacin treatment failure, while not common, did occur, suggesting antimicrobial susceptibility in MG merits careful monitoring.
O02.5 A Phase II, Dose Ranging Study to Evaluate the Efficacy and Safety of Single-Dose Oral Solithromycin (CEM-101) For Treatment of Patients with Uncomplicated Urogenital Gonorrhoea
Authors: Hook E W , Jamieson B D , Oldach D , Harbison H , Whittington A , Fernandes P 
Published: July 2013

ObjectivesEmerging resistance to available treatment creates an urgent need for new therapies for uncomplicated gonorrhoea. Solithromycin, a new 4th generation macrolide with 3 ribosomal targets, is highly active against most antibiotic-resistant strains ofNeisseria gonorrhoeae. A Phase II, dose ranging study to evaluate the efficacy and safety of single-dose oral solithromycin for uncomplicated urogenital gonorrhoea was conducted.MethodsConsenting participants with suspectedNeisseria gonorrhoeaeinfection were cultured at the urethra/cervix, rectum, and pharynx at enrollment and Day 7.The primary outcome was bacterial eradication (conversion from positive baselineN. gonorrhoeaeurethral/cervical culture to negative) at Day 7. Secondary outcomes included eradication of rectal or pharyngeal gonorrhoea and the eradication of gonococcal and chlamydial nucleic acids. Initially, eligible patients received a single 1200 mg oral dose of solithromycin; following demonstration of bacteriologic efficacy, a second cohort was treated with a single 1000 mg dose.ResultsOf 41 (19 M, 22 F) participants enrolled, 28 were treated with a 1200 mg dose and, to date, 13 with 1000 mg. Gonococcal eradication rates in 22 evaluable 1200 mg patients were 100% (22/22) for urethral/cervical, pharyngeal (5/5), and rectal (2/2) infections. Of 9 evaluable 1000 mg patients enrolled to date, gonococcal eradication rates have been 100% (9/9) for urethral/cervical, pharyngeal (2/2), and rectal (1/1) infections. Susceptibility data from 25 isolates show the median MIC (range) for solithromycin was 0.06 µg/mL (0.015–0.125) and for azithromycin was 0.125 µg/mL (0.06–0.5).Solithromycin was generally well-tolerated with mild dose-related gastrointestinal AEs (68%; 28/41). The most common AE was mild diarrhoea, occurring in 61% (17/28) of patients receiving the 1200 mg dose and 15% (2/13) of patients receiving the 1000 mg dose.ConclusionsA single dose of 1200 or 1000 mg solithromycin appears to be well-tolerated and effective in eradicatingN. gonorrhoeae.
O02.6 Azithromycin Versus Doxycycline For the Treatment of Genital Chlamydia Infection - a Meta-Analysis of Randomised Controlled Trials
Authors: Hocking J , Kong F , Vodstrcil L , Guy R , Chen M , Fairley C , Bradshaw C , Tabrizi S 
Published: July 2013

IntroductionThere has been considerable debate questioning the efficacy of azithromycin for the treatment of genital chlamydia. We conducted a meta-analysis to compare the efficacy of 1 gramme azithromycin with 100mg doxycycline twice daily for seven days for the treatment of genital chlamydia infection.MethodsMedline, PubMed, Embase and the Cochrane Controlled Trials Register were searched till end 2012. Inclusion criteria included (1) randomised controlled trial of azithromycin versus doxycycline for the treatment of urethral or cervical chlamydia, and; (2) evaluation of microbial cure within 3 months of treatment. Type of diagnostic test, duration of follow up, gender, patient status (all symptomatic versus both symptomatic/asymptomatic) and microbial cure were extracted. The primary outcome was difference in efficacy (doxycycline efficacy minus azithromycin efficacy) at final follow up. Meta-analysis calculated a pooled efficacy for each treatment and the difference in efficacy between treatments.ResultsOf 692 references identified, 23 trials met the inclusion criteria. 1065 individuals were treated with azithromycin and 850 with doxycycline; all studies reported efficacy within 6 weeks follow-up. Pooled cure rates were 96.2%(95% CI: 94.2%, 98.3%) for azithromycin and 98.1%(95% CI: 96.6%, 99.7%) for doxycycline. The pooled efficacy difference was 1.9%(95% CI: 0.4%, 3.4%) showing a small but significant difference in favour of doxycycline; there was negligible heterogeneity between studies (I2 = 1.9%, p = 0.44). There was no difference in efficacy in men (3.8%; 95% CI:-1.2%, 8.8%) or women (–0.9%; 95% CI: –5.3%, 3.6%). When stratified by type of test, efficacy was significantly higher for doxycycline in culture-based studies (1.8%; 95% CI: 0.4%, 3.3%), but not in NAAT-based studies (5.5%; 95% CI: –2.1%, 13.1%). Efficacy was higher for doxycycline in symptomatic men (6.3%; 95% CI: 3.0%, 12.3%), but not in symptomatic women (–4.5%; 95% CI: –14.9%, 5.9%).ConclusionThese results suggest that doxycycline may be more effective than azithromycin for the treatment of urethral or cervical chlamydia infection, especially in symptomatic men.
O03.2 Antimicrobial Resistance of Neisseria Gonorrhoeae in the European Union: Response to the Threat of Multidrug Resistant Gonorrhoea
Authors: Spiteri G , Cole M , Unemo M , Hoffmann S , Ison C , Laar M van de 
Published: July 2013

BackgroundIncreasing reports of Neisseria gonorrhoeaein vitrodecreased susceptibility and resistance, and treatment failures with third generation cephalosporins are of major concern as these drugs are the last remaining options for effective antimicrobial therapy in many settings.MethodsThe European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), a sentinel surveillance programme funded by the European Centre for Disease Prevention and Control since 2009, monitors antimicrobial susceptibility patterns across the European Union (EU/EEA). Participating laboratories performed susceptibility testing by Etest or agar dilution breakpoint method, or sent isolates to reference laboratories in Denmark, Sweden or the United Kingdom for testing. Euro-GASP validated proficiency and result accuracy through an external quality assessment scheme.ResultsIn 2011, 1902 isolates from 21 countries were collected and tested. The percentage of tested isolates with decreased susceptibility to cefixime (8.0%) remained stable compared to 2010 (8.7%), but was still significantly higher than in 2009 (5.1%, p < 0.01). Isolates with decreased susceptibility to cefixime were reported from 17 countries in 2011, the same as in 2010; however three countries reported such isolates for the first time in 2011. For the first time, ten isolates with decreased susceptibility to ceftriaxone were reported from two countries. Rates of ciprofloxacin (49%) and azithromycin (5.3%) resistance remained high. Minimum inhibitory concentration of gentamicin remained low (MIC50: 4 mg/L; MIC90: 8 mg/L).ConclusionsAlthough the rapid increase and spread of decreased susceptibility to cefixime in 2010 has not continued, the detection of isolates with decreased susceptibility to ceftriaxone is concerning. ECDC has published a response plan which aims to strengthen surveillance of gonococcal antimicrobial susceptibility in the EU/EEA; ensure that capacity for culture and susceptibility testing is maintained; establish a system for collection and verification of data on clinical treatment failure; and to recommend public health actions at national and European level.
O05.1 High Grade Anal Intraepithelial Neoplasia: One Virus, One Lesion
Authors: Richel O , Quint K D , Lindenman J , Noesel C M Van , Koning M N C De , Munckhof H A M Van den , Vries H J C De , Prins J M , Quint W G V 
Published: July 2013

BackgroundPrevention and treatment of anal intraepithelial neoplasia (AIN) in HIV+ men who have sex with men (MSM) is subject of discussion. Knowledge on causative HPV types is crucial in understanding AIN and in vaccination studies. However, data on AIN-specific HPV are limited and whole tissue sections (WTS) often show multiple HPV infections.In this study, we analysed whether WTS and subsequent laser capture micro-dissection (LCM) with HPV PCR genotyping accurately detects type-specific HPV DNA in individual areas of high grade (HG)AIN.Methods31 WTS with HGAIN of 21 HIV+ MSM were analysed by the SPF10 PCR/LiPA25 (version 1) HPV genotyping system. In case of multiple HPV types, PCR was repeated in selected areas of AIN, isolated by LCM.ResultsWTS PCR showed a single HPV type in 17 (55%). In the remaining 14 WTS sections with multiple HPV types, PCR was repeated in LCM-isolated dysplastic areas (median: 4 per WTS). In 12 of 14 these samples, the number of HPV types could be reduced to single HPV types within discrete areas of a lesion, resulting in a total of 29 (17+12), in which (components of) HGAIN show a singe HPV type. HPV 16 was found in 14/29 (48%), HPV 18 in 3 and HPV 58 in 3. The remaining HPV types that could be linked to a lesional area were HPV 26, 31, 35, 39, 52, 53, 54, 59, 67, 68/73, 74, 91 and one indeterminate HPV type.ConclusionWTS PCR and subsequent LCM PCR is accurate in detecting lesion specific HPV types in AIN and it seems that 94% of the AIN-lesions (on macroscopic or microscopic level) are caused by a single HPV type. Apart from HPV 16, the predominant type, a wide range of other HPV types are responsible for HGAIN, which has consequences for vaccination development.
O05.3 More Than Meets the Eye: A Molecular Phylogenetic Analysis Reveals Importance of Novel Bacteria in Bacterial Vaginosis (BV)
Authors: Srinivasan S , Morgan M T , Liu C , Matsen F A , Hoffman N G , Fiedler T L , Agnew K J , Marrazzo J M , Fredricks D N 
Published: July 2013

BackgroundBV is a highly prevalent dysbiotic condition associated with adverse reproductive and health outcomes in women. BV is marked by loss of certain lactobacilli and acquisition of complex communities of anaerobic bacteria. Gram stain is the gold standard for diagnosis, wherein the abundances of four bacterial morphotypes are assessed; Lactobacillus, Gardnerella, Bacteroides and Mobiluncus. Newly described uncultivated bacteria are highly specific for BV, but no studies have investigated the association between these bacteria and Gram stain morphotypes.MethodsWe examined the association of bacteria detected by broad-range 16S-rRNA gene PCR/pyrosequencing with bacterial morphotypes detected in Gram stains from 220 women with and without BV. We also used species-specific quantitative PCR and fluorescence in situ hybridization (FISH) methods to document concentrations of two bacteria with curved rod morphologies:Mobiluncusspecies and the uncultivated BV-associated bacterium-1 (BVAB1).ResultsWe provide evidence that curved Gram-negative rods designated Mobiluncus morphotypes by Gram stain are more likely BVAB1. Rank abundance plots of vaginal bacteria in women with curved rods (Nugent 9–10) showed that BVAB1 was the dominant bacterium (26%), while relative abundance ofMobiluncuswas only 0.2%. BVAB1 sequence reads were also associated with Mobiluncus morphotypes (p = 7.4E-06). Among women with Nugent scores 9–10, the mean concentration of BVAB1 DNA was 2-log units greater thanMobiluncus(p < 0.001). FISH analyses also revealed that among women with Nugent scores of 10, the mean number of BVAB1 cells was greater thanMobiluncuscells (p < 0.001). In addition, we noted thatPrevotellaandPorphyromonasspp. are significantly associated with the Bacteroides morphotype, whereasBacteroidesspecies are rare.ConclusionsGram stain morphotype designations for BV need revision to account for novel vaginal bacteria. These findings have major implications for studies using Gram stains as a proxy to describe the vaginal microbiota.
O06.4 Using SMS Text Reminders to Reduce ‘Did Not Attend’ (DNA) Rates in Sexual Health and HIV Appointment Clinics
Authors: Brook G , Farmer T , Murphy S , McSorley J 
Published: July 2013

BackgroundDNA rates in sexual health and HIV clinics have historically been high and this can reduce the ability of the clinic to see patients within the UK national target of two working days. The availability of technology such as SMS texting allows appointment reminders to be readily sent just prior to the appointment.ObjectivesTo measure the impact of the SMS text appointment reminders on the DNA rates in a clinic providing sexual health and HIV appointments.MethodsDNA rates were measured for two 2-month periods before (2009) and after (2012) the introduction of routine SMS text reminders being sent to patients who have pre-booked appointments. Texts were sent two working days before the booked appointments.ResultsOverall, after the introduction of SMS text appointment reminders, the DNA rates fell by 35% from 203/768 (26%) to 119/699 (17%), P < 0.0001. The fall was especially large for male sexual health appointments: 56/200(28%) vs 24/165 (15%), P < 0.004 a fall of 46%. Female sexual health DNA rates also fell: 69/302(23%) vs 43/273(16%), P < 0.02, a fall of 30%, as did DNA rates for HIV clinics: 78/266(29%) vs 52/261(20%), P < 0.001, a fall of 31%ConclusionsSMS texts sent to patients two days before a booked appointment reduced the DNA rate by an average of one in three. The decrease was especially large for male patient appointments. Routine text reminders for appointments are an effective way of ensuring that the clinic runs efficiently.