bluuebunny/crossref_metadata_2025 huggingface dataset:
S06.2 Using Social Media For Partners Services in Adolescents
Authors: Rietmeijer C A M
Published: July 2013

Partner notification (PN) and treatment is a cornerstone of STI prevention. In the U.S., face-to-face, patient-initiated or provider-assisted partner notification has shown to result in approximately 50% of patients referring at least one partner for evaluation and treatment. While to some this percentage is higher than expected, there is considerable room for improvement. A number of developments in the past decade have shown promise in enhancing PN. Expedited partner treatment, i.e., providing medications to partners without an intervening medical consultation, has been proven to decrease re-infections among index patients above and beyond traditional partner notification and this practise is now widely endorsed. Second, the Internet has provided the technical means to enhance communication between providers, patients and their partners that could result in a higher proportion of notified contacts. Internet-based interventions include simple email or text messages to the partner, either directly from the patient or from health-department staff (if agreed to by the index patient), outreach in chat rooms on gay websites, stand-alone online partner notification programmes, and interventions using social networking sites. While the online possibilities appear to be limitless, especially for adolescents who are very engaged in the online environment, there are few interventions that have been formally evaluated. This presentation aims to provide and overview of online programmes for partner services and a review of studies that have attempted to evaluate them. So far, it appears that few online interventions have risen above the “proof-of-concept” and their overall effectiveness may be limited. In addition, a number of studies have indicated that the majority of STI-infected patients prefer to notify their partner in person rather than using text or email messages. While research into effective online interventions for PN and treatment should continue, this must not come to the detriment of high-quality, in-person PN practises.
S06.3 MSM Partner Services: What Works?
Authors: Steben M , Taylor D , Cheuk E
Published: July 2013

Background

Partner notification (PN) is an important public health activity in STI control to stop onwward transmission. Various forms of PN services have been developed but not all have been evaluated to the same extent. In the era of evidence-based resource allocation, it is of utmost importance to focus limited resources on services shown to be the most efficient and effective.

Methods

A review of the current literature and of the National Collaborating Centre for Infectious Diseases (NCCID) STBBI partner notification (PN) project productions was conducted. The impact of these various forms of PN services on disease incidence, re-infection, relationship status and healthcare costs will serve as efficiency and effectiveness markers.

Results

Outcomes of MSM PN services has been measured and found to be associated with

reduced index case GC and CT reinfection rates through patient delivered therapy,

higher adoption of safer sexual practises in both index case and their partners,

reduced incidence of STIs,

higher rates of notification to long term partners and significant partners,

high acceptability of face-to-face patient delivered partner notification in significant or long term relationships compared to higher acceptability of physician or electronic notification for casual or anonymous partnerships

lower cost per case reached by patient referral compared to provider referral,

lower levels of stress in relationships. Emotional and physical abuse after PN services can occur. The fears accompanying PN services can affect sexual spontaneity.

Caution should be used before discarding PN services when efficiency or effectiveness is low because epidemiologic insight can still be gathered to help redirect screening activities.

Conclusions

A Review of the evidence indicates that MSM PN services works!
S06.4 New Directions in HIV Partner Services: An Evolving Model of Global, Integrated Field Services
Authors: Golden M
Published: July 2013

Partner services are a longstanding component of public health efforts to control sexually transmitted infections (STI). However, they have not been a consistent part of HIV prevention efforts either in high-or lower-income nations. In many areas, partner services for HIV and other STIs have been administratively separated, and the goals of partner services have usually been narrowly conceived to concentrate exclusively on the diagnosis and treatment of sex partners. This is now beginning to change. New evidence suggests that HIV PS in high income nations may be less effective at finding new cases of HIV than previously believed, but could play an important role in linkage to care. In sub-Saharan Africa, HIV PS appears to be highly acceptable and effective.

This session will focus on new opportunities in the area of HIV PS. The speaker will review the following issues: (1) data supporting the efficacy of HIV partner services as an HIV case-finding tool in both in high and low-income nations; (2) cost and cost-effectiveness data on HIV PS; (3) evidence that PS for bacterial STIs can been used to promote HIV case-finding and engagement in care among persons with previously diagnosed HIV infection; and (4) outstanding research questions related to HIV PS.
S07.1 Insights into Maternal Gonorrhoea: Human Primary Cervical and Amniochorionic Epithelial Cell Responses to Neisseria Gonorrhoeae Infection
Authors: Edwards J L , Gawthorne J A , Edwards T J
Published: July 2013

Bacterial infection is widely recognised as a factor contributing to adverse pregnancy outcomes (APOs).Neisseria gonorrhoeaeinfections continue to be a universal and intractable problem. In this regard, maternal gonorrhoea increases a woman’s risk for APO by 6.5-fold. Bacterial infection is thought to trigger a pro-inflammatory response that initiates those processes involved in (preterm) human parturition. The ability of gonococci to invade and transcytose amniotic sac tissues,in vivo, is inferred from the ability to isolate gonococci from these tissues and from amniotic fluid. However, there are currently no data to indicate how gonococcal infection can result in APO, and a physiologically relevant human model of pregnancy that is amendable to scientific analyses has hindered elucidation of factors contributing to APO. Thereby, an understanding of gonococcal infection as it relates to human pregnancy, usinghumancell models of disease, could provide new insights into the pathophysiology of gonococcal disease and of APO as they likely occurin vivo. To this end, we investigated gonococcal infection under conditions reflecting normal pregnancy by using primary epithelial cells derived from the human cervix (i. e. pex cells) and amniochorionic membranes (i. e. pace cells) and by altering the combined concentrations of pertinent steroid hormones. Comparative, quantitative, infection assays indicated that gonococci adhere to and invade amniochorionic cells and tissue, which was further observed to occur by a complement receptor-mediated mechanism. We demonstrate thatN. gonorrhoeaeinfection of pex and pace cells elicits the differential production of nitric oxide and complement proteins, as well as the specific matrix metalloproteases, prostaglandins, and cytokines thought to participate in triggering the onset of human parturition. Hence, we provide the first direct evidence to indicate a potential link between gonococcal infection and the induction of APOs.
S07.2 The Extrusion Paradigm of Chlamydia Pathogenesis
Authors: Hybiske K
Published: July 2013

Chlamydiais the most commonly reported bacterial disease in the United States, and remains the leading bacterial cause of sexually transmitted infection, responsible for approximately 90 million new STI cases annually worldwide. Of particular concern is that infections withC. trachomatiscan lead to severe medical complications in women, such as pelvic inflammatory disease and ectopic pregnancy. Alarmingly, there remain fundamental gaps in our understanding ofChlamydiapathogenesisin vivo, for example their natural course of infection in humans and why protective immunity is not established. To help address these questions, our laboratory has been interested in determining howChlamydiadisseminate within the host. Our original discoveries elucidated the mechanisms by which chlamydiae exit host cellsin vitro. Surprisingly,Chlamydiapossess two mechanisms for cellular escape that are mutually exclusive: (i) Extrusion, a packaged release ofChlamydiain which the vacuole pinches off and exits the cell within a membrane-encased compartment; this leaves the original host cell intact, often with a residual chlamydial inclusion. (ii) Lysis, a destructive process that is mediated by proteases and the sequential rupture of vacuole, nuclear and plasma membranes, culminating in the release of free bacteria. The maintenance of two discrete exit mechanisms underscores the fundamental importance of this process for intracellular pathogens such asChlamydia. Extrusions are novel pathogenic structures that we hypothesise confer unique means of interacting with the host’s innate immune system, enabling immune evasion and promoting tissue dissemination. To this end, we have recently illuminated key characteristics of chlamydial extrusions that allow direct infection of new cells and their engulfment by professional phagocytes. Bacteria within phagocytosed extrusions are protected from macrophage killing mechanisms for at least 8 h. These results have important implications forChlamydiapathogenesisin vivo, including dissemination, transmission and the elicitation of immune responses.
S07.3 Survival Strategies of Haemophilus Ducreyi: Role of Transporters
Authors: Rinker S D , Bauer M E
Published: July 2013

During human disease, Haemophilus ducreyi leads a primarily extracellular lifestyle, in which the organism is under constant pressure from the immune system. To survive in this environment, H. ducreyi expresses multiple mechanisms that counteract various antimicrobial activities of innate immunity. Key among these is secretion of LspA proteins to prevent phagocytosis, allowing H. ducreyi to reside extracellularly. When phagocytes cannot engulf bacteria, they secrete granule contents, including antimicrobial peptides (APs) such as cathelicidin and defensins, to kill the pathogens extracellularly. APs bind and destabilise cell membranes to lyse bacteria. Our laboratory is studying two transporter systems that protect H. ducreyi from human APs, including cathelicidin LL37 and beta-defensins. To prevent lethal interactions between LL37 and the inner membrane, H. ducreyi utilises the Sap (sensitive to antimicrobial peptides) transporter, which takes up periplasmic LL37 for cytoplasmic degradation. By mutagenizing structural components of the Sap transporter, we have found a direct correlation between the effectiveness of Sap-mediated LL37 resistancein vitroand the contribution of the transporter to virulence in humans. Further, we found that H. ducreyi OppA (oligopeptide binding protein A), the periplasmic component of another uptake transporter, appears to cooperate with the Sap transporter for LL37 uptake. For beta-defensin resistance, H. ducreyi utilises the MTR efflux transporter. MTR is a member of the resistance-nodulation-division family of multidrug resistance transporters that pump hydrophobic agents from the periplasm and cytoplasm out of the cell. Our data demonstrate that the H. ducreyi MTR transporter confers resistance to both LL37 and beta-defensins. Interestingly, we also found that the MTR transporter affects activation of CpxRA, which globally regulates virulence factors in H. ducreyi. The role of MTR in human virulence is under investigation. Together, these studies highlight the significance of AP resistance mechanisms to pathogen survival in the human host.
S07.4 Identification of Determinants Triggering Antigenic Variation inMycoplasma Genitalium
Authors: Burgos R , Totten P A
Published: July 2013

Mycoplasma genitalium(MG) is an emerging sexually transmitted pathogen associated with reproductive tract disease in men and women. Despite the development of a robust antibody response, MG can persist for months to years, potentially increasing the risk for sexual transmission and serious upper reproductive tract infection in women. The molecular basis of MG pathogenesis is poorly understood, in part due to its fastidious nature, extremely small genome lacking known virulence genes, and the limited genetic tools available for molecular investigations. Nevertheless, previous studies have linked MG virulence to its unique terminal organelle, a complex structure that mediates adherence, motility, and cell division. The terminal organelle is composed of a complex array of unique proteins, including MgpB and MgpC which serve as major adhesins and are required for terminal organelle biogenesis. Remarkably, these two surface-exposed proteins also undergo phase and antigenic variation through a unique process of segmental recombination between discreet variable regions withinmgpB andmgpC and multiple homologous archived sequences, termed MgPa repeats (MgPar). Our goal is to identify the molecular factors required to promote this genetic diversity, a mechanism which likely contributes to the ability of MG to adapt to different host conditions and maintain persistent infections. Recently, we have shown that RecA is required formgpB/C gene variation and that this protein is expressed in several isoforms. We have now expanded these studies by showing that these RecA isoforms originate from different translational start sites and that specificrecA upstream sequences regulate the expression ratio of these isoforms andmgpB/C-MgPar recombination. Together, these studies suggest the presence of novel regulatory mechanisms that may allow this genetically challenged organism to cause disease, evade the host immune response, and persist in infected individuals.
S07.5 Understanding Dissemination ofTreponema PallidumWithin the Host - is There Hope For a Syphilis Vaccine?
Authors: Houston S , Hof R , Wetherell C , Phillips A , Denchev Y , Cameron C E
Published: July 2013

Treponema pallidumis a highly invasive spirochete that disseminates to organ sites distal to the site of primary infection and is able to cross both the blood-brain and placental barriers during the course of infection. The corkscrew motility used byT. pallidumundoubtedly contributes to its invasive nature. However, this signature motility is shared with other spirochetes and thus the factors responsible for the widespread dissemination capability that is unique toT. pallidumremain unknown. We have identified the treponemal-specific, surface-localised protein pallilysin as a dual functioning adhesin/metalloprotease that exhibits specific attachment to, and degradation of, multiple extracellular matrix components. Pallilysin is produced as an inactive proprotease that can be activated via either autocatalytic cleavage or host-originating thrombin cleavage. Purified recombinant pallilysin, as well as a non-invasive model treponeme heterologously expressing pallilysin on its surface, exhibit specific degradation of fibrin clots. Pallilysin immunisation alters the course ofT. pallidumdissemination following challenge within the rabbit model of syphilis infection, with immunised rabbits exhibiting a reduced bacterial burden within organs distal to the site of challenge compared to unimmunized control rabbits. Further, rabbit infectivity tests (RIT) showed that rabbits receiving lymph nodes from challenged, unimmunized rabbits seroconverted and developed orchitis by 30 days post-transfer, while 66% of RIT rabbits receiving lymph nodes from challenged, pallilysin-immunised rabbits remained seronegative and had no signs of orchitis at the termination of the experiment (day 185 post-transfer). Collectively these studies identify pallilysin as aT. pallidum-specific metalloprotease that (1) exploits the host coagulation cascade to facilitate protease activation, (2) plays a central role in treponemal dissemination and (3) shows promise as a novel syphilis vaccine candidate.
S08.1 Treatment of Gonorrhoea in an Era of Emerging Cephalosporin Resistance and Results of a Randomised Trial of New Potential Treatment Options
Authors: Kirkcaldy R D
Published: July 2013

Background

Cephalosporins are the mainstay of recommended gonorrhoea treatment, and there is an urgent need for treatment options for cephalosporin-allergic patients or infections with suspected cephalosporin resistance. We evaluated the efficacy and tolerability of two novel combinations of existing antimicrobials for treatment of uncomplicated urogenital gonorrhoea.

Methods

We conducted a non-comparative trial, randomising patients with urogenital gonorrhoea to one of two regimens: gentamicin 240 mg intramuscularly plus azithromycin 2 g orally (GENT/AZI), or gemifloxacin 320 mg orally plus azithromycin 2 g orally (GEMI/AZI). The primary outcome was microbiologic cure of urogenital infections (negative follow-up culture) at 10–17 days post-treatment. All participants who returned for follow-up and had evaluable follow-up cultures were included in this per protocol analysis.

Results

For 401 evaluable participants (GENT/AZI-202; GEMI/AZI-199), the mean age of both groups was 30 years. Most participants were heterosexual men (GENT/AZI, 57%; GEMI/AZI, 51%), followed by men who have sex with men (GENT/AZI, 33%; GEMI/AZI, 39%), and women (GENT/AZI, 9%; GEMI/AZI, 11%). Microbiological cure was achieved by 100% (lower one-sided 95% confidence interval, 98.5%) of GENT/AZI participants, and 99.5% (lower one-sided 95% confidence interval, 97.6%) of GEMI/AZI participants. GENT/AZI cured 10/10 pharyngeal and 1/1 rectal infections; GEMI/AZI cured 15/15 pharyngeal and 5/5 rectal infections. In the GENT/AZI arm, the most common adverse events (AEs) were mild-moderate nausea (27% of participants), diarrhoea (19%), abdominal discomfort/pain and vomiting (both 7%). In the GEMI/AZI arm, the most common AEs were nausea (37% [8% moderate-severe]), diarrhoea (23%), and abdominal discomfort/pain (11%).

Conclusions

Both study regimens were highly effective. Gastrointestinal AEs, especially nausea and diarrhoea, were common. These results provide alternative gonorrhoea treatment options for patients who cannot be treated with cephalosporins.
S08.2 Is Azithromycin the Best Treatment For Chlamydia?
Authors: Radcliffe K
Published: July 2013

Azithromycin has been widely used for many years as first-line therapy for chlamydial infection (or as equal first-line with doxycycline). However, there are now several reasons to reconsider its position.

Firstly, although earlier trials showed azithromycin to have cure rates which were high and equivalent to those of doxycycline, more recent studies have found it to have lower, and inadequate, levels of success in women with cervical infection, men with urethral infection, and for rectal infection in both men and women.

Secondly, the increasing recognition of the importance ofMycoplasma genitaliumas a pathogen, especially as an important cause of urethritis in men. In the absence of a readily available test forM. genitalium, men with non-gonococcal urethritis are often treated with a single dose of azithromycin, which is known to be a less effective treatment forM. genitaliumthan is doxycycline. As a result many such men have persistent symptoms following such treatment, requiring repeat visits and further antibiotic therapy. Their sexual partners may also require further treatment. Additionally, there is evidence that single-dose azithromycin therapy (as against longer courses) can induce resistance inM. genitalium.

Thirdly, the widespread use of azithromycin is probably leading to increasing resistance to this agent in other infections where it has a place; especially in gonorrhoea where it is now widely recommended as an adjunct to ceftriaxone in the belief that this will reduce the likelihood of resistance to ceftriaxone developing, but also in the treatment of syphilis where azithromycin has a role as a second-line agent e.g. in cases of allergy to penicillins.
S08.3 Mycoplasma Genitalium and Chlamydia Trachomatis in Laparoscopically Diagnosed Pelvic Inflammatory Disease
Authors: Bjartling C , Osser S , Persson K
Published: July 2013

Introduction

Pelvic inflammatory disease (PID) is a well known complication of infection withChlamydia trachomatis(C.trachomatis). The knowledge ofMycoplasma genitalium(M.genitalium) and its role in PID is relatively limited. In this study we report on the proportions ofC.trachomatisandM.genitaliumattributable to PID from an ongoing study of laparoscopically diagnosed cases of PID.

Method

Women seeking care at the emergency service at the Department of Obstetrics and Gynaecology at Malmo University Hospital in Sweden from 2004 through the mid of 2012 with clinically suspected PID, who underwent diagnostic laparoscopy, were eligible. Specimens from the cervix/and or vagina together with abdominal fluid were collected and analysed for pathogens such asC.trachomatisandM.genitalium.

Results

In all, 208 women were included and 123 (59.1%) were diagnosed with PID at laparoscopy.C.trachomatiswas present in cervix and/or abdominal fluid in 29/123 (23.6%) of these cases.M.genitaliumwas present in cervix and/or abdominal fluid in 5/123 (4.1%) cases of PID. In three of these casesM.genitaliumwas positive only in cervix and there was a dual infection withC.trachomatispositive in the abdominal fluid. Two PID cases wereM.genitaliumpositive only, (2/123, 1.6%). A significantly declining trend forC.trachomatisPID was observed (42.8% - 11.5% p = < 0.001). The prevalence ofC.trachomatisandM.genitaliumwas 2.8% and 2.1% respectively in 5519 women tested from 2003 to 2008 in the same clinic.

Conclusion

The over all proportion of PID attributable toC.trachomatiswas 23.6% but over the study period a significantly declining trend was seen. The proportion of PID attributable toM.genitalium(1.6%) was significantly lower considering the prevalence to be in the same range as forC.trachomatis, suggesting thatM.genitaliumwas a less aggressive pathogen in terms of clinical manifestations of PID.
S08.4 Mycoplasma Genitalium: Implications For Disease, Treatment and the Public Health
Authors: Jensen J S
Published: July 2013

M. genitaliumis an established cause of sexually transmitted urethritis and cervicitis, and may cause upper tract disease in women. Detection by nucleic acid amplification tests is currently the only diagnostic method available, but no FDA approved assays are currently available, and the CE marked tests suffer from limited clinical evaluation.

In most settings,M. genitaliuminfections explain 15–25% of symptomatic non-gonococcal urethritis, but as diagnosis of the infection is not routinely carried out, treatment will usually be syndromic. However, only a few randomised trials have evaluated treatment ofM. genitalium, and compared only doxycycline 200 mg daily for 7 days with a 1 g single dose of azithromycin. Together with results from open trials, it is obvious that doxycycline is inefficient in eradicatingM. genitaliumshowing eradication rates around 35%. The eradication rate after azithromycin 1 g single dose is significantly better, but differs greatly between studies. Thus, older studies appear to have higher eradication rates than recent ones and a lower eradication rate is reported in studies from centres where azithromycin has been used as the primary treatment for chlamydial and idiopathic urethritis and cervicitis.

At present, the only second line antibiotic that has been shown to have a high activity against macrolide resistantM. genitaliumis moxifloxacin. However, this drug is significantly more expensive and has a less favourable safety profile than macrolides, and multidrug resistant infections have emerged, primarily in patients with contact to South East Asia. Consequently, there is an urgent need for clinical trials with possible alternative drugs. Such trials should preferably also address the treatment efficacy in chlamydial and idiopathic urethritis and cervicitis as a single treatment covering these conditions would be advantageous.
S09.2 Neisseria Gonorrhoeae: Are We Exerting the Selective Pressure?
Authors: Ison C A
Published: July 2013

Treatment of gonorrhoea has historically been delivered by a single dose of a highly effective antimicrobial agent, to which resistance is not documented, to aid compliance and break transmission. Resistance inNeisseria gonorrhoeaecompromises this approach and occurs both by acquisition of plasmids or chromosomal DNA from other bacteria orNeisseriaspp or by selection of mutants resulting from misuse or overuse of antimicrobial agents, such as long term use of a single agent.

Resistance to ciprofloxacin, a fluoroquinolone, illustrates the effect of both misuse of earlier generations of quinolones and of suboptimal doses, as well as overuse. Quinolones target the DNA gyrase and topoisomerase enzymes that are responsible for DNA supercoiling and any interference with this process is bactericidal. Ciprofloxacin was widely used, often at low doses because of its high efficacy, but resistance emerged quickly resulting from selection of mutants, altering the target site and giving increasing drifts to resistance. Azithromycin, a macrolide which binds to 23S rRNA component of the 50S ribosome and interferes with protein synthesis, is effective against multiple STIs and therefore the selective pressure for resistance has been considerable. Although low-level resistance emerged quickly, high-level resistance inN. gonorrhoeae, resulting from a single point mutation in the peptidyltransferase loop of domain V of the 23S rRNA gene, was only reported in recent years and threatens to compromise its use. Sporadic use of spectinomycin selected for high-level resistance in a single step, which appears clonal and has not spread widely. Limited use of the aminoglycoside, gentamicin, for which the efficacy data is weak, appears to remain clinically active.

In this era of multi-drug resistant gonorrhoea it is imperative that the selective pressure exerted by continual use of a single agent is understood and clinical practise modified, where necessary, to prevent gonorrhoea becoming untreatable.
S09.3 Herpes Simplex Virus
Authors: Frobert E , Ducastelle-Lepretre S , Casalegno J , Nave V , Eibach D , Lina B , Morfin F
Published: July 2013

The more and more frequent and widespread use of acyclovir (ACV), but also the increasing number of immunocompromised patients might induce an increase in HSV (Herpes Simplex Virus) resistance. HSV resistance to ACV is mainly associated with mutations in the thymidine kinase (TK) gene although mutations in the DNA polymerase can be observed. Up to now, resistance of HSV to ACV was a major concern for immunocompromised patients with a frequency between 2.5 and 10%. This study aimed to reassess HSV resistance to ACV, during a ten year period, in immunocompetent and in immunocompromised patients (bone marrow transplant patients, solid organ transplant, HIV positive patients, cancer patients). From 2002 to 2011, 1538 patients positive for HSV were tested for the susceptibility of their virus to ACV (1044 immunocompetent and 494 immunocompromised). In immunocompetent patients, prevalence of resistance remains under 0.5%, whatever the period studies. In immunocompromised patients, a significant increase can be observed, from 4.3% during 2002–2006 (11/255 patients) to 13.4% during 2007–2011 (32/239) (p = 0.0002). This significant increase is mainly observed among bone marrow transplant patients in which the prevalence is 10% (5/52) during 2002–2006 and 38% (30/79) during 2007–2011 (p = 0.0002), whereas other types of immune deficiencies do not show an increase (1.3% versus 2.9%, p = 0.2). New chemotherapy protocols (FLAMSA) and type of transplantation as blood cord transplant are part of the explanation. Genotyping of the resistant viruses (35 viruses) reveal mutations in the TK gene for 80% of them. Double population including resistant and susceptible viruses were recovered in 5 isolates (5/34 = 14%). Rapid diagnosis of HSV resistance, but also research on alternative treatment are more than ever of interest.
S09.4 Mycoplasma Genitalium
Authors: Jensen J S
Published: July 2013

M. genitaliuminfections explain 15–25% of symptomatic male NGU and causes sexually transmitted urethritis, cervicitis, and PID in women. The bacterium is extremely difficult to isolate by culture, and consequently, the knowledge about antimicrobial resistance and its underlying molecular mechanisms has been slow to accumulate.

In the few randomised trials ofM. genitaliumconducted to date, doxycycline has been compared with a 1 g single dose of azithromycin, and together with results from open trials, it is evident that doxycycline is inefficient in eradicatingM. genitaliumwith eradication rates around 35%. The eradication rate after azithromycin 1 g single dose has most often been significantly higher, but differs greatly between studies. Remarkably, older studies appear to have higher eradication rates than the more recent ones, and in the latest study from the US, no significant difference between doxycycline and azithromycin efficacy could be detected.

Although several mutations have been associated with increased macrolide MIC in strains selected by passage in the presence of macrolides, only mutations in the 23S rRNA gene at position 2058 and 2059 (E. colinumbering) have been detected in patients failing azithromycin treatment.

A number of rapid methods for detection of such mutations directly from clinical samples have been developed and have proved to be clinically useful in directing treatment. Pre-treatment mutations have been found in between 10–15% of contemporary samples where doxycycline is used as the primary NGU treatment and is most commonly around 40% in settings where azithromycin is the primary drug. However, in Greenland where chlamydial infections are extremely common and azithromycin is used liberally, mutations have been found in nearly 100% of the specimens tested.

At present, moxifloxacin is the only second line antibiotic that has a proven high efficacy against macrolide resistantM. genitalium. However, price and safety profile as well as the emergence of multidrug resistant strains emphasises the urgent need for clinical trials with alternative drugs.
S10.1 Predicting the Social and Behavioural Consequences
Authors: Hogben M S , Ford J V
Published: July 2013

Recent data from HIV prevention trials conducted with sero-discordant couples suggest that HIV transmission drops when the infected individual is taking anti-retroviral medications (ARV). However, there is potential for unintended social and behavioural consequences of this and other interventions. Using the HIV treatment cascade as a lens, the review will cover individual and population-level data in HIV and STD prevention research with a view to identifying such consequences of intervention. Although the focus will be upon risk compensation as a potential consequence of HIV treatment, the review will also attend to potential positive social and behavioural consequences.

With respect to data from which to predict social and behavioural consequences, the majority of HIV and STD prevention interventions are conducted through small groups or on a one-to-one basis (e.g., in clinical settings), rather than at the population level. Most are concerned explicitly with risk reduction behaviours or address the behaviours essential to successful biomedical intervention. Population-level interventions are rarer, but do include communication campaigns and efforts to affect HIV or STD through social determinants. With respect to risk compensation, some studies explicitly address risk compensation, while others have sufficient behavioural follow-up data from which to measure it - the unintended measurement of unintended consequences. Fewer studies permit one to attribute effects to different potentialcausesof risk compensation, including risk homeostasis, overestimation of protection, or the intentional resumption of previous behaviour patterns.

The final part of the review is devoted to approaches that seek to minimise negative consequences or to maximise positive consequences, the latter arising when an intervention gives people hope where they once had little or none, and leading to further individual efforts to protect themselves and others (including changes in risk homeostasis). Positively-framed communication campaigns in particular may accelerate efforts and further population-level protective action and health promotion.
S10.2 Determining Uptake, Adherence, & Patterns of ART Use as Prevention
Authors: Cohen M S
Published: July 2013

Selected antiretroviral treatment (ART) of HIV reduces the concentration of virus in genital secretions. In one randomised controlled trial and most (but not all) observational studies ART reduced the sexual transmission of HIV. Some (but not all) ecologic studies suggests that broader, earlier antiviral treatment of HIV may reduce incidence of HIV in some (but not all) at risk populations. A compelling long-term study from South Africa demonstrated a direct relationship between increased availability of ART in communities and decreased incidence of HIV. However, the maximal benefit of HIV “treatment for prevention” will likely require a programme of universal “test and treat”, where most HIV infected patients are identified, linked to care, and treated very early in disease and for life. It seems likely that for maximal public health benefit ART must be started immediately regardless of CD4 count, and so the personal benefit and safety of immediate ART must be transparent. In some settings (especially where MSM are most likely to be infected) it may be necessary to find and treat people with acute and early HIV infection, a difficult challenge. To better understand the maximal benefits of this approach the early treatment of IDU and sex workers are also being studied, since these populations contribute to the spread of HIV. Community randomised trials designed to examine the feasibility of the implementation of treatment for prevention are underway. Treatment of a far greater number of people early in disease will be cost effective or cost saving in most settings, and can offer macroeconomic benefit as well. The mass treatment of HIV-the current centrepiece of HIV prevention- is best seen as a bridge to ever simpler therapy or a cure.
S10.3 Modeling the Effect of TAP on the HIV/AIDS Epidemic
Authors: Garnett G P
Published: July 2013

Background

The efficacy of ARV treatment that achieves viral suppression in dramatically reducing HIV infectiousness is proven. What is less clear is the implications for the best use of treatment in programmes, how treatment should and could be scaled up and wheat the effectiveness of treatment use in programmes will be across populations.

Methods

Review of observational data on the impact of treatment programmes on HIV incidence and deaths and mathematical models exploring the impact of existing and proposed programmes.

Results

Mathematical models show that HIV treatment can reduce HIV incidence, but this reduction depends upon who is treated, the success of the programme maintaining viral suppression in those treated and on patterns of risk behaviour. Observations of the impact of treatment programmes on the spread of HV at a population level show mixed impacts with competing interpretations and implications for future programmatic development. Treatment guidelines emphasise the treatment of those who probably contribute least to onward transmission of HIV and more work is required to understand local epidemiology and design treatment programmes accordingly.

Conclusions

Future, studies of the impact of treatment as prevention should concentrate on how to implement at scale treatment programmes and maximise reductions in incidence. Using HIV treatment as an HIV prevention intervention promises a major step forward in responding to the HIV pandemic, but taking success for granted could generate unsustainable programmes with perverse outcomes.
S11.1 Sexual Behaviour in Britain in the New Millennium: A New Era?
Authors: Mercer C H
Published: July 2013

Background

In 2001, Britain’s second National Survey of Sexual Attitudes and Lifestyles (Natsal-2) demonstrated increased sexual risk behaviour in contrast to Natsal-1, undertaken a decade earlier. STI diagnoses also increased between the mid-1990s and the mid-2000s, but since then, increases have been more modest. These trends coincided with changes in sexual health policy and practise in Britain, resulting in greater STI testing and the use of more sensitive diagnostic tests, making STI surveillance data less indicative of risk behaviour. This paper reviews a range of evidence to examine whether, and if so how, sexual behaviour has changed in Britain since the start of the millennium.

Methods

Analyses of routine data (including STI surveillance data, census data), general population surveys (including Natsal, Health Survey for England 2010 (HSE-2010), British Social Attitudes surveys), and community surveys of men-who-have-sex-with-men (MSM, including London’s Gay Men’s Sexual Health Surveys).

Results

Demographic trends support the limited sexual behaviour data collected experimentally by HSE-2010 suggesting that increases in heterosexual risk behaviour observed between 1990 and 2000 have not been sustained since 2000. At the same time, there has been increasing tolerance in Britain of more diverse sexual lifestyles, with public attitudes towards homosexuality increasingly liberal. While the population prevalence of recent same-sex behaviour in 2010 remains around 2–3%, among MSM, the proportion reporting high-risk sexual practises continues to rise, especially among HIV-positive MSM, as evident from increasing HIV incidence and STI outbreaks among this core-group.

Conclusions

Increases in sexual risk behaviour among MSM in Britain have clearly been observed since 2000, however, definitive conclusions regarding changes in heterosexual behaviour are limited until methodologically-comparable data are available from Natsal-3. These new data will enable us to better examine hypotheses regarding changes in the British population’s sexual behaviour across time and across the life-course.
S11.2 Sex in the United States in the New Millennium: Temporal Trends Among Men and Women Aged 15–44 Years
Authors: Leichliter J S , Haderxhanaj L T , Chesson H W , Aral S O
Published: July 2013

Background

Examining national trends in sexual behaviour can aid in the understanding of STD trends. We examined trends in sexual behaviour, focusing on sub-populations most impacted by STDs in the US.

Methods

We used data from the 2002 and 2006–10 National Survey of Family Growth (NSFG), a multi-stage survey nationally representative of men and women aged 15–44 years living in the United States (US). The sample sizes and response rates for the surveys were 12, 571 (79%) in 2002 and 22,682 (77%) in 2006–10. Sexual behaviours included in this analysis were predominantly from audio computer assisted self-interview and were compared by several demographics, separately by sex. Data were weighted to represent the US population and data analyses accounted for the multi-staged sampling procedures used by NSFG.

Results

Sexual behaviours with opposite- and same-sex partners were frequently similar in 2002 and 2006–10. Of women who ever had vaginal sex, there was no change in the average number of partners in the past 12 months (1.21 in 2002, 1.11 in 2006–10); however there was a slight decrease over time for Hispanic and black women and a slight increase among women in the non-Hispanic other category. Findings for men were similar except for a slight increase in partners among white men. Overall, HIV-related risk with opposite-sex partners decreased from 2002 to 2006–10. Specifically, exchanging sex for money or drugs significantly decreased among women (2.0% to 0.7%, p < 0.05) and men (2.6% to 1.3%, p < 0.05). Finally, the average number of male partners decreased among sexually active men who have sex with men (MSM) from 2.9 in 2002 to 2.3 in 2006–10 (p < 0.05). Specific HIV risk also declined among MSM.

Conclusion

Preliminary findings suggest that behaviours have not changed much during this time; however, we did identify shifts in behaviours among sub-populations.
S11.3 Switzerland: National Trends in Sexual Behaviour in the Context of HIV/STI Behavioural Surveillance 1987–2012
Authors: Dubois-Arber F , Jeannin A , Lociciro S , Bize R , Spencer B , Gervasoni J
Published: July 2013

Background

National trends in sexual behaviour have been assessed mainly in the context of the HIV related behavioural surveillance system set up in Switzerland between 1987 and 1992.

Methods

Several populations are included in the system. Repeated surveys have been regularly conducted among the general population and youth, men having sex with other men (MSM), injecting drug users (IDU). Data on sexual behaviour are regularly recorded among people living with HIV/Aids (PLWHA) included in the Swiss HIV Cohort.

Results

The main trends observed are :

In young adults (aged 18–20):

a steady increase in the proportion of sexually active at age 17

a stable median number of partners with a recent increase in the proportion of multipartners;

a high and stable level of condom use among multipartners.

Among MSM:

an increase in the number of partners and a steady increase in unprotected anal intercourse since 1997, after a period of decreasing trends.

Among IDU:

a low and stable use of condoms with stable partners;

a high and stable use of condoms with occasional and paying partners (only among women) with a possible recent decreasing trend.

Among PLWHA: a high use of condoms with all types of partners with a recent decrease.

Conclusions

The behavioural surveillance system in place allowed to assess various trends in sexual behaviour in several populations such as: long term trends regarding sexual debut, stable trends and recent changes regarding different indicators of sexual activity in the general population, IDU and PLWHA, inversion of trends in sexual activity and condom use among MSM.
S12.1 Human Papillomavirus Vaccines - Correlates of Protection Are Not Defined
Authors: Williamson A
Published: July 2013

Specific types of human papillomavirus (HPV) are causally associated with cervical cancer, with at least 99% of cervical cancers having detectable HPV DNA. Other cancers that also have an association with HPV include anogenital and oropharyngeal malignancies affecting both males and females. Over two thirds of these cancers are associated with HPV types 16 and 18, which are the high-risk types targeted by the HPV vaccines Gardasil and Cervarix. Gardasil also protects from infection with HPV-6 and HPV-11, which cause genital warts and recurrent respiratory papillomatosis. The vaccines are based on the major capsid protein, L1, which self assembles into virus-like particles. Although HPV L1 is a relatively conserved gene with different HPV types having L1 sequence homology of up to 90%, the vaccine induced protection is HPV type-specific. Both vaccines induce excellent protection against the specific types targeted; however, there is also limited protection from infection with closely related HPV types. The vaccines do not cause regression of established genital lesions: regression is due to cell-mediated immunity. The serological correlates of protection of the vaccines are not defined but it is likely that protection is largely due to neutralising antibodies: animal studies have shown that protection can be transferred by passive immunisation with immune sera. In natural infections, titres of HPV antibodies are much lower than for vaccine induced antibodies, and in fact not all infected people develop detectable antibodies. It is likely that serological correlates of protection will become better defined only if vaccine induced protection starts to wane as the antibody titres potentially drop over time; it may then be possible to define levels of antibody needed for protection. Such information could inform the need for further booster vaccinations.
S12.2 Tales of Woe: HSV Vaccine and Null Study Results
Authors: Wald A
Published: July 2013

Herpes simplex virus type 2 (HSV-2) infects 530 million people, is the predominant cause of genital ulcer disease, and a key driver of HIV epidemic in subSaharan Africa. In human populations with susceptibility to HSV appears universal. In animal models, several candidate preventative and therapeutic vaccines have been successful only to fail in clinical trials, including recent null results from the prophylactic glycoprotein D2 subunit vaccine trial. However, detailed analyses of the immune suggest assays that antibody response may correlate with protective immune response, providing the first evidence of immune correlate of protection from infection. In addition, recent characterization of CD8 tissue memory cells in genital mucosa suggests that we may also identify immune correlate of HSV-2 control in the infected host. In this Symposium, I will discuss HSV-2 vaccine efforts in the context of our understanding of pathogenesis and epidemiology, as well as the current pipeline of candidate vaccines.
S12.3 Understanding How Broadly Cross-Neutralising Antibodies Develop in HIV Infection - Clues For HIV Vaccine Development?
Authors: Morris L
Published: July 2013

Neutralizing antibodies are likely to play a crucial role in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralising (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develops these antibodies after many years. Thus understanding how these antibodies evolve could provide a template for HIV vaccine design. To date we have studied ∼80 HIV-infected individuals in the long-term CAPRISA cohort and found that approximately a quarter develop cross-neutralising antibodies by 3 years of infection. Analysis of longitudinal samples showed that breadth developed gradually starting from year 2, with the number of viruses neutralised as well as the antibody titer increasing over time, peaking at 4 years post-infection with little activity thereafter. The extent of cross-neutralising activity correlated with CD4 T cell decline and viral load at 6 months post infection, suggesting that early events set the stage for the development of breadth. Mapping of the epitopes targeted by cross-neutralising antibodies revealed that in most cases they recognised one of the 4 well-defined sites of vulnerability on the HIV envelope. This included the two glycan-dependent epitopes in the V2 and C3 regions of gp120, the CD4 binding site as well as the membrane-proximal external region (MPER). Isolation of monoclonal antibodies from some of these individuals has confirmed the plasma specificities and revealed interesting insights into antibody ontogeny. Furthermore, we have shown how viral escape from earlier strain-specific antibodies contributes to the formation of neutralising antibody epitopes highlighting the dynamic interplay between viral and antibody evolution. Our ongoing work aims to more precisely define the changes in the antibody and viral repertoires that accompany the development of broadly cross-neutralising antibodies with the aim of mimicking these events in a vaccine scenario.