bluuebunny/crossref_metadata_2025 huggingface dataset:
O15.4 Field Performance of the Alere Determine HIV Combo Assay in a Large Australian Multi-Centre Study in a Sexual Health Clinic Setting
Authors: Conway D P , Holt M , McNulty A , Couldwell D L , Smith D E , Davies S C , Cunningham P , Keen P , Guy R
Published: July 2013

Background

Rapid HIV testing has been available to gay and other men who have sex with men (MSM) overseas for many years. Alere’s Determine HIV Combo ‘fourth generation’ rapid test containing antibody and antigen components is now available in Australia, but field performance data for this assay are limited.

Methods

From September 2011, MSM attending four Sydney public sexual health clinics were offered rapid HIV testing using the Determine HIV Combo and also had sexually transmissible infection screening and conventional HIV serology. Rapid test sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated by comparing results to reference tests (Abbott Architect HIV Ag/Ab Combo, Biorad Genscreen HIV antigen and HIV Western blot).

Results

In 15 months, 1716 men had 2043 rapid tests performed with four invalid rapid tests (0.2%) excluded from analysis. Of 34 men confirmed as HIV-positive by national HIV case definitions, 29 had reactive rapid tests (sensitivity = 85.3%, 95% CI: 68.2–94.5). With 29 true reactive rapid tests from a total of 44 reactive tests, PPV overall was 65.9% (50.0–79.1). Of five men with false non-reactive tests, four were seroconvertors. Rapid tests were non-reactive in 1990 out of 2005 cases where laboratory HIV testing was negative; hence, overall specificity was 99.3% (95% CI: 98.7–99.6) and NPV was 99.8% (99.4–99.9). Of 15 men with false reactive rapid tests, four had non-specific reactivity on HIV Western blot. Specificity and NPV for the antibody component was 99.5% (99.0–99.7) and 99.9% (99.6–100.0) and for the antigen component was 99.8% (99.4–99.9) and 99.6% (99.1–99.8), respectively.

Conclusion

Antibody and antigen component specificity was consistent with the rapid test package insert; whereas sensitivity was lower, notably in those with recent infections. Hence, identifying patients at risk of recent infection is vital so that conventional laboratory serology is performed. A formal assessment of test performance in seroconvertors is warranted.
O15.5 Performance Characteristics of SD Bio Line Rapid HIV-Syphilis Duo Test Kit For Simultaneous Detection of HIV and Syphilis Infections
Authors: Ondondo R O , Odoyo J B , Bukusi E A
Published: July 2013

Background

Human immunodeficiency virus (HIV) andTreponema pallidumshare modes of transmission. Congenital syphilis is a significant cause of stillbirth, prenatal death and serious neonatal infections. We sought to evaluate rapid test kit for HIV-syphilis dual detection to improve diagnosis and enable accurate management towards achieving the renewed zeal of eradicating syphilis and congenital syphilis.

Methods

Six hundred and eighty serum specimens from HIV discordant couples in a clinical trial, tested for syphilis infection by RPR with reactive specimens confirmed by TPHA, were used for this evaluation. HIV status was determined by Uni-Gold™ and Determine™ HIV rapid kits and all positive samples confirmed by two HIV Enzyme immunoassay test. These specimens were blindly retested using the HIV-Syphilis Duo kit.

Results

Of 698 samples evaluated 139 (20%) were RPR positive and 346 (50%) were HIV positive. Among the RPR positive, 85 (61%) were TPHA positive. None of 559 RPR negative samples tested syphilis positive on HIV-Syphilis Duo kits. Of the 85 RPR positive-TPHA positive samples, none tested syphilis negative on the HIV-Syphilis Duo kit. All RPR positive-TPHA negative samples tested syphilis negative on the HIV-Syphilis Duo kit. Sensitivity and specificity was: both 100% for syphilis detection and; 99.71% and 100% respectively for HIV detection. On this sample set the Sensitivity of Determine™ and Uni-Gold™ was 96.82% and 98.27% respectively while the Specificity was 93.75% and 99.43% respectively. HIV-Syphilis Duo kit detected 5 early HIV infections that were missed out by Determine™ and Uni-Gold™ at least one month prior to a seroconversion visit.

Conclusion

HIV-Syphilis DUO test kit performed better compared to RPR for syphilis and Determine™ for HIV detection. It was equivalent to TPHA for syphilis and Uni-Gold™ for HIV detection. Its implementation in antenatal clinics/VCTs will present an added opportunity for simultaneous diagnosis of HIV and syphilis.
O15.6 Molecular Surveillance ofNeisseria GonorrhoeaePenicillin Resistance: Informing Empiric Prescribing Policy in Western Australia
Authors: Speers D J , Goire N , Mak D , Fisk R
Published: July 2013

Against the worldwide trend, there remain populations in the remote regions of Western Australia (WA) where the efficacy rates for penicillin may be above the World Health Organisation (WHO) 95% guideline forN. gonorrhoeadrug selection. Oral amoxicillin (3g) with probenecid (1g) is used empirically in these regions. The majority of gonorrhoea diagnoses in our laboratory are performed by PCR with culture-based antimicrobial resistance surveillance limited by the lack of a representative number of isolates. We therefore implemented a world-first comprehensive molecular gonococcal surveillance of penicillin resistance in our remote populations.

We tested allN. gonorrhoeae-PCR positive cases from August 2011 to July 2012 (n = 1235) using a PCR assay targeting the penicillinase-producingN. gonorrhoeae(PPNG). This represented approximately 60% of the 2092 notified WA gonorrhoea cases but 91% of cases from the remote regions. Of these regions, the Kimberley PPNG rate was 0.7%, the Pilbara 4.0%, the Goldfields 10.3%, and the Mid West 0% compared to Perth, the state capital city with 12(8–16)%. When adjustments were made for chromosomal-mediated penicillin resistance (additional 3.4%), the Kimberley and Mid West regions remained below the 5% WHO resistance threshold for penicillin. In addition, a review of the Pilbara and Goldfields regions found PPNG only in the major regional centres.

Based on this data, continuation of amoxicillin with probenecid in the Kimberley region with its reintroduction into the Mid West was recommended. In the Pilbara and Goldfields amoxycillin with probenecid could be continued in remote communities but empiric treatment in the regional centres and of non-locals should employ intramuscular ceftriaxone therapy, as for other parts of WA. Our study shows that molecular surveillance of gonococcal antimicrobial resistance directly from clinical specimens is feasible and could be extended to include other targets conferring resistance to other antibacterials such as ceftriaxone.
O16.2 Strain Typing to Resolve RepeatedChlamydia TrachomatisInfections in Young Heterosexual Dutch Populations
Authors: Götz H M , Bom R J M , Wolfers M , Fennema J S A , Broek I V F van den , Speksnijder A G C L , Bruisten S M
Published: July 2013

Repeated infections ofChlamydia trachomatis(CT) occur frequently in young adults. These may be new infections, or persistent infections due to treatment failure or unresolved infections in sex partners. We compared CT multilocus sequence typing (CT-MLST) toompAgenotyping in discriminating new from persistent Chlamydia infections. Samples from young heterosexual persons were selected from Dutch screening implementation studies in Amsterdam and Rotterdam, the Netherlands, between 2009 and 2011. Paired CT positive samples at baseline (T0) and after 6 months (T1) were genotyped with 6 MLST loci which included:ompA,CT046,CT058,CT144,CT172andCT682. The uniqueness of Chlamydia strains was assessed by adding samples from 256 heterosexuals in Amsterdam.

For 27 out of 34 persons with repeated infections, full MLST types were obtained for paired samples. In 17 of these 27 persons a multilocus (n = 13) or single locus variant (n = 4) was found, indicating new CT infections at T1. For 5 MLST discordant participants, theompAgenovar was identical. The 10 persons with concordant typing results were categorised as treatment failure (5 persons) or unresolved infections (5 persons). A minimum spanning tree, generated from all cases and 256 reference samples showed large and small clusters and singletons. Surprisingly, the persons with concordant samples had CT strains that were either unique (singleton) or found in small clusters. The median time between T0 and T1 did not differ between the persons with concordant and discordant samples. The number of sex partners before T0 however, was higher for the discordant group. High resolution sequence typing was superior compared toompAtyping in discriminating new from persisting Chlamydia infections. Many persons (37%) showed exactly the same Chlamydia strain after 6 months indicating possible treatment failure.
O16.3 Controlling Chlamydia: Population Modeling to Assess Promising Interventions
Authors: Glasser J W , Owusu-Edusei K , Glick S N , Aral S O , Gift T L
Published: July 2013

Background

Chlamydia is an important public health problem associated with neonatal sequelae, pelvic inflammatory disease, infertility, and ectopic pregnancy.

Methods

Using a population model with 2 genders and ages 15–44 years in 5-year groups, but only heterosexual contacts, we evaluated the impact of actual and hypothetical interventions on chlamydia in the U.S. Parameters were obtained from the literature or estimated from the National Health and Social Life Survey and Seattle Sex Survey. The model was calibrated by adjusting gender-specific probabilities of infection on contact. We calculated the basic reproduction number (R0), defined as the average number of secondary infections per infectious person in a wholly-susceptible population without interventions. We also calculated the age- and gender-specific equilibrium prevalence and contributions to R0. And we assessed the impact of interventions by comparing reproduction numbers with and without them. To assess the feasibility of opportunistic screening, we analysed Market Scan, a commercial health insurance database, to determine the proportion of people seeking medical care.

Results

Treating symptomatic men and women who seek care and screening 38% of women aged 15–24 years during annual examinations more than halve the reproduction number. The equilibrium age- and gender-specific prevalence of infection match those observed in the National Health and Nutrition Examination Survey. Men cause more secondary infections than women (contributing twice as much to R0in some age groups), and people aged 25–29 years cause as many as those aged 20–24. Analysis of the Market Scan database indicates that insured men seek care often enough for screening to have substantial impact. Screening women reduces the reproduction number by 3%; screening a similar proportion of young men would reduce it another 4%.

Conclusions

Our modelling suggests that screening men as well as women and extending the upper age to 29 years may affect chlamydia transmission or sequelae.
O16.4 Human Papillomavirus in Very Young Men Who Have Sex with Men and the Potential Benefit from Vaccination
Authors: Zou H , Morrow A , Tabrizi S , Grulich A , Garland S , Hocking J , Bradshaw C , Prestage G , Fairley C , Chen M
Published: July 2013

Background

Homosexually active men are at increased risk for human papillomavirus (HPV) infection and HPV associated anal cancer. Prophylactic HPV vaccines have maximum efficacy in people who have not already been infected with HPV. This study aims to determine the prevalence of HPV among teenage MSM.

Methods

Same sex attracted males aged 16 to 20 were recruited in Melbourne via clinics, universities, community events, media, social networking and peer recruitment. At baseline, 3, 6, and 12 months anal and penile swabs and an oral rinse were obtained to test for 37 HPV genotypes.

Results

200 men were recruited. At baseline 39% had at least one type of HPV DNA detected from at least one site. High risk (HR), low risk (LR) and quadrivalent vaccine (QV) preventable types were detected in 31% (95% CI: 25–37%), 30% (95% CI: 24–37%) and 23% (95% CI: 17–29%) of men respectively. Multiple types of any, HR, LR and QV preventable HPV were detected in 27%, 13%, 11% and 8% of men respectively. The site specific prevalence of any HPV detected from the oral cavity, penis and anus were 2%, 9% and 31% respectively: the prevalence of QV preventable types at these 3 sites was 0.5%, 4% and 20% respectively. Anal HPV was absent in 27 of 30 men who reported never receiving anal sex. Additional results of serology for HPV 6/11/16 and 18 will also be presented.

Conclusion

In this study, the first to focus on early HPV acquisition among teenage MSM, HPV was common but in the minority. HPV vaccination prior to the onset of sexual activity is ideal; however, short of universal vaccination of school aged males, selected vaccination of teenage same sex attracted young men could still prevent many infections.
O16.5 Concordance of Anal, Penile, and Oral Human Papillomavirus Hr-HPV Infections and HPV Seropositivity in HIV-Infected and HIV-Negative Men Who Have Sex with Men: The HIV & HPV in MSM (H2M) Study
Authors: Rijn V M van , Mollers M , Mooij S H , Speksnijder A C G L , King A J , Vries H J C de , Klis F R M van der , Melker H E de , Sande M A B van der , Loeff M F Schim van der
Published: July 2013

Background

Infection with human papillomavirus (HPV) is not generally followed by seroconversion for reasons not yet fully understood. This cross-sectional study investigated concordance between high-risk (hr) HPV infections at three anatomical sites and concordant seropositivity, in both HIV-infected and HIV-negative men who have sex with men (MSM).

Methods

MSM aged ≥ 18 years were recruited from the Amsterdam Cohort Studies, an STI clinic and an HIV treatment centre in Amsterdam, the Netherlands. The associations between anal, penile, and oral HPV infections and concordant seropositivity of 7 hr-HPV types (16, 18, 31, 33, 45, 52 and 58) were estimated using generalised estimating equations (GEE) regression analyses.

Results

Among the 306 HIV-infected MSM 93% were hr-HPV seropositive (i.e. seropositive for at least one of the 7 hr-HPV types) and 69% were infected with at least one anal, penile, or oral hr-HPV infection. Of 441 HIV-negative MSM 74% were hr-HPV seropositive and 41% were infected with one or more hr-HPV infections. Type-specific hr-HPV seropositivity was not more likely for men with concordant infections at multiple anatomical sites (OR 1.58, 95% CI 1.06–1.86) compared to those with concordant infections at only one anatomical site (OR 1.45, 95% CI 1.22–1.73). In multivariable analysis, adjusting for key demographic and sexual behavioural factors, type-specific hr-HPV seropositivity was associated with concordant anal hr-HPV infections (OR 1.60, 95% CI 1.32–1.92), but not with concordant penile (OR 0.79, 95% CI 0.58–1.06) or oral (OR 1.36, 95% CI 0.85–2.17) hr-HPV infections; in stratified analyses, these associations were similar for HIV-infected and HIV-negative men.

Conclusions

In both HIV-infected and HIV-negative MSM, anal hr-HPV infections were associated with hr-HPV seropositivity, while penile and oral hr-HPV infections were not. Our findings support the hypothesis that seropositivity differs by the type of epithelium infected, implying that mucosal infection may provide a stronger signal to the immune system.
O16.6 Pre-Vaccination Seroprevalence of 15 Human Papillomavirus (HPV) Types Among Slovenian Women Screened For Cervical Cancer
Authors: Klavs I , Učakar V , Jelen M M , Faust H , Dillner J , Poljak M
Published: July 2013

Background

Our objective was to estimate the seroprevalence of 11 high-risk (hr) HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59) and four low-risk (lr) HPV types (HPV 6, 11, 68, 73) among Slovenian women screened for cervical cancer before the introduction of vaccination against HPV.

Methods

3259 serum specimens from the Slovenian HPV prevalence survey were tested for HPV type-specific antibodies with a multiplexed pseudovirion-based serological assay (PsV-Luminex).

Results

Seropositivity for any of the 15 HPV types was 65.7%, any of the 11 hr-HPV types 59.2%, and any of the four lr-HPV types 33.1%. Antibodies against multiple HPV types were more common (45.3%) than against single HPV types (20.4%). Antibodies against at least one of the four vaccine HPV types (HPV 6, 11, 16, and 18) were detected in 40.8% women. Among hr-HPV types seropositivity was the highest for HPV 16 (25.2%) and among lr-HPV types for HPV 6 (19.1%). Age-specific seropositivity for HPV 16 was the highest among 30–39 years old women (29.6%) and decreased with increasing age to 14.0% among 60–64 years old women (p = 0.014). Seropositivity for any of the hr-HPV among women with pathological cytology was 76.8% and those negative for intraepithelial lesion or malignancy 58.3% (p < 0.001).

Conclusion

Our results show a substantial burden of lifetime sexual exposure to these 15 HPV types before the introduction of vaccination and also a relatively high cumulative exposure to at least one of the four vaccine HPV types. Thus, vaccination of females before sexual debut with a quadrivalent HPV vaccine has a potential to contribute to a substantial reduction of the burden of cervical infections and cervical cancer as well as some other HPV related morbidity, including genital warts. Our data also present the baseline for monitoring HPV long-term vaccination impact.
O17.2 HIV Prevention at Scale: Has It Worked? Evaluation of the Impact of the Avahan Programme in South India
Authors: Pickles M , Boily M , Vickerman P , Lowndes C M , Moses S , Blanchard J F , Ramesh B M , Paranjape R S , Alary M
Published: July 2013

Background

Avahan, the India AIDS initiative of the Bill & Melinda Gates Foundation, is the largest targeted HIV preventive intervention in the world. We examine evidence for its overall impact, and estimate HIV infections averted acrossAvahandistricts.

Methods

A mathematical model of HIV transmission among high-risk groups and the general population was developed. It was parameterised using data from serial cross-sectional surveys (IBBAs) within a Bayesian framework, to reproduce HIV prevalence trends amongst female sex workers (FSWs), their clients, and men who have sex with men (MSM) in 24 South Indian districts. We test whether these prevalence trends are more consistent with self-reported increases in consistent condom use (CCU) followingAvahan,or a counterfactual assuming CCU increased at slower pre-Avahanrates. To assess this we used a Bayes factor, which also measures strength of evidence for the impact estimates. Using regression analysis, the prevention impact in the IBBA districts is extrapolated to allAvahandistricts.

Results

In 13/24 districts, modelling suggests medium to strong evidence for the large self-reported increase in CCU sinceAvahanimplementation. Elsewhere evidence is weaker, with CCU generally already high pre-Avahan. Approximately 32,700 HIV infections (95% credibility interval 17,900–61,600) were averted over four years in IBBA districts with moderate/strong evidence. Adding districts with weaker evidence increases this to 62,800 (32,000–118,000), and extrapolation suggests that 202,000 (98,300–407,000) infections were averted across all 69Avahandistricts in South India, increasing to 606,000 (290,000–1,193,000) over ten years. Over four (ten) years, 42% (57%) of HIV infections were averted.

Conclusion

This is the first evaluation ofAvahanto account for the causal pathway of the intervention, changing risk behaviour in FSWs and MSM to avert HIV infections in these groups and the general population. The findings suggest considerable impact can be achieved from targeted behavioural HIV prevention initiatives.
O17.3 Do We Need to Vaccinate Males Against HPV?
Authors: Ali H , Korostil I , Guy R J , Wand H , Grulich A E , Read T R H , Regan D G , Fairley C K , Donovan B
Published: July 2013

Background

From mid-2007 Australia funded a universal HPV vaccination programme for young females, which achieved high coverage rates. In 2013, Australia has become the first country to extend the HPV vaccination programme to boys aged 12–13 years. A catch-up programme includes boys aged 14–15. The aim of this study was to look at the current and expected impact of the vaccination programme on genital warts in men.

Methods

Eight Australian sexual health services provided data on all new patients. We compared trends in proportion of patients diagnosed with genital warts in the pre-vaccination (2004 to mid-2007) and vaccination (mid-2007 to 2011) periods. Furthermore, we used a mathematical model of HPV transmission to predict the impact of male vaccination on the incidence of genital warts.

Results

In the pre-vaccination period, there was no change in proportion of men diagnosed with genital warts. In the vaccination period, there were significant declines in proportions of < 21 (81.8%, compared to 92.6% decline in women) and 21–30 year old (51.1%, compared to 72.6% in women) heterosexual men diagnosed with genital warts; from 12.1% in 2007 to 2.2% in 2011 and from 18.2% in 2007 to 8.9% in 2011 respectively. There was no significant decline in diagnosis in men > 30 years of age, or in homosexual or bisexual men. Results of the model are in-line with this decline in men. With the introduction of male vaccination programme, the model predicts a much lower incidence, approaching elimination, in coming decades.

Conclusion

Although there has been a decline in the proportion of young heterosexual men diagnosed with genital warts suggesting herd immunity, the decline is slower than that of young females and no decline is observed in homosexual/bisexual men. The male vaccination programme will lead to near elimination of genital warts in both females and males in Australia.
O17.4 Evaluating the Cost Effectiveness of Targeted Vaccination Strategies to Reduce Incidence of HPV-Related Cancer and Other Clinical Outcomes in Men Who Have Sex with Men (MSM) in British Columbia, Canada
Authors: English K M , Marra F , Davoudi B , Gilbert M , Pourbohloul B
Published: July 2013

Background

Of late, there has been discussion around the potential for vaccinating males in addition to the routine female human papillomavirus (HPV) vaccination programme against cervical cancer. While men who have sex with women (MSW) will likely receive some protection from female vaccination, men who have sex with men (MSM) remain vulnerable. Incidence rates of vaccine preventable cancers are disproportionately represented among MSM.

Methods

Based on the natural history of infection progression for HPV subtypes 6, 11, 16 and 18, mathematical transmission dynamics and cost-effectiveness analysis models were developed to assess the prevalence and incidence of these subtypes among the MSM population in the Greater Vancouver Area, British Columbia, Canada. Model parameters, demographic, and epidemiological data were informed from provincial data and the literature.

We simulated three additional vaccination strategies, in combination with the current programme (Grade 6 schoolgirls (with 70% vaccine coverage)): first, vaccination of Grade 6 boys (with 70% vaccine coverage); second, vaccinating 18-year old self-identified MSM (with 25, 50 or 75% vaccine coverage); and finally, vaccinating any MSM within the vaccine-approved age range (with 25, 50 or 75% vaccine coverage).

Results

There is significant variability of cost estimates associated with clinical outcomes related to the HPV vaccine-preventable strains in the literature. Our sensitivity analysis indicates that the implementation of any scenario tested is incrementally cost effective, assuming a baseline of the current girls-only immunisation programme. On average, overall incidence of anal, penile, and oropharyngeal cancer cases attributable to vaccine-preventable strains will be reduced by approximately 90%, within 50 years, and given effective prophylaxis and lifelong immunity.

Conclusion

All targeted MSM immunisation scenarios tested were cost-effective by averting high costs related to each cancer case avoided and given the relatively low number of vaccine doses required within this population, compared to the male population at large.
O17.6 Expanded HIV Testing Program in STD Clinics Fails to Impact Diagnosis of New HIV-Positive Cases
Authors: Klein P W , Messer L C , Leone P A , Miller W C
Published: July 2013

Background

The Centers for Disease Control recommends routine HIV testing in clinical settings. The evidence for an increase in HIV diagnoses as a result of these testing programmes is inconclusive. We examined the North Carolina (NC) expanded HIV testing programme’s impact on HIV testing and the diagnosis of new HIV-positive cases in sexually-transmitted disease (STD) clinics.

Methods

The NC expanded HIV testing programme implemented routine, opt-out HIV testing in STD clinics in November 2007. All persons aged 18–65 who were tested for HIV in NC STD clinics July 2005-June 2011 were analysed. The monthly change in the number of HIV tests performed, number of new HIV-positive cases identified, and HIV positivity proportion per 1000 tests before and after the intervention were evaluated. Interrupted time series analysis with autoregressive components was used to account for underlying temporal trends and autocorrelation.

Results

From July 2005-June 2011, 414,612 HIV tests were performed, yielding 1293 new HIV cases (0.3%). Prior to the intervention, the number of HIV tests performed increased by 60 tests per month (rate difference [RD] = 60.4, 95% confidence interval [CI]: 50.6, 70.2). However, after the intervention, the monthly increase in testing slowed to 42 tests per month (RD = 41.7, 95% CI: 36.8, 46.6). After the introduction of the intervention, neither the number of new HIV-positive cases identified nor the HIV positivity per month differed from expected case detection trends without the intervention (number of new HIV-positive cases: RD = –0.11, 95% CI: –0.33, 0.11; HIV positivity per 1000 tests: RD = 0.04, 95% CI:-0.001, 0.073).

Conclusion

Despite the introduction of an expanded HIV testing programme in NC STD clinics, no change in HIV testing or HIV case detection was observed. A lack of evidence for programme yield in a clinical setting with high baseline levels of HIV testing questions the intervention’s appropriateness.
O18.1 Molecular Techniques For Differentiation of theT. PallidumSubspecies and Specimen Collection with FTA Elute Cards
Authors: Chen C , Chi K , Pillay A
Published: July 2013

Introduction

The causative agents of venereal syphilis (Treponemasubsp.pallidum), yaws (subsp.pertenue), and bejel (subsp.endemicum) are indistinguishable on the basis of morphology, syphilis serology and existing diagnostic PCR. Our objective was to develop a real-time (rt) multiplex PCR assay that can simultaneously detect all three organisms in a single tube. In addition, we evaluated the potential use of FTA Elute cards for collection of skin lesion specimens for molecular testing.

Methods

Serial dilutions of purified genomic DNA fromT. pallidumwere spotted onto FTA cards and air dried. Cards were stored at ambient temperature (∼23oC) for up to 1 month. DNA was eluted from a 6-mm disc and tested by apolAPCR, a rt PCR for macrolide point mutations in the 23S rRNA gene, and the CDC typing method (PCR/RFLP analysis oftprandarp). The rt triplex PCR targets thetp858andtp0620genes and the assay was evaluated using DNA from 25 strains ofT. pallidum, 14 strains ofT.pertenue,and 2 strains ofT. endemicum.

Results

The rt triplex PCR distinguished all three subspecies and had an analytical sensitivity of 1–10 genomic copies using purified DNA fromT. pallidumstrain Nichols. The detection limit ofpolArt PCR was approximately 10–100 genomic copies/6-mm disc. The molecular subtype and azithromycin susceptibility genotype was easily determined using the spiked FTA cards.

Conclusions

The rt triplex PCR is a specific and sensitive assay for differentiation of theT. pallidumsubspecies and should be useful in areas where both syphilis and yaws or bejel are endemic and, in determining the extent of yaws worldwide. The FTA Elute card provides a simple way to collect, store and transport specimens at ambient temperature in the absence of a cold chain and involves minimal sample processing prior to molecular testing.
O18.2 ‘3 in 1’ Study: Pooling Self-Taken Pharyngeal, Urethral and Rectal Samples into a Single Sample
Authors: Sultan B J , Fish R , Carrick G , Gilson R , Brima N , Robinson A , Mercey D , White J , Benn P
Published: July 2013

Background

APTIMA Combo 2 (AC2) reliably detectsChlamydia trachomatis(CT) andNeisseria gonorrhoeae(NG) at extra-genital sites in men who have sex with men (MSM), but testing three separate samples (pharynx, urethra, rectum) is costly. Self-taken pharyngeal and rectal samples can be added to first-void urine (FVU) and tested as a single pooled sample (PS). We compared the sensitivity of PS with individual sample testing (SOC), and its acceptability to patients. In addition sample processing methods were compared (Method A: swabs and FVU into universal container to laboratory; Method B: APTIMA urine tube spiked with swabs to laboratory).

Methods

MSM (symptomatic or CT/NG contacts) were recruited at two clinics. All were tested by PS and SOC; order of sampling was randomised. Demographics, sexual behaviour, symptoms, signs and acceptability were collected. Any positive AC2 test was considered a true positive. Each clinic used one processing method (not randomised).

Results

627/700 planned MSM recruited to date (43% HIV+); 65% symptomatic; 43% unprotected anal sex in the last month. 94 CT and 189 NG infections were detected (prevalence of CT and/or NG 46%; dual infection 6%). The sensitivity of PS and SOC to detect CT and NG was 92% and 96% respectively (p = 0.68). PS failed to detect 22 infections (CT = 6; 1 pharynx, 4 rectum, 1 urethra, and NG = 16; 11 pharynx, 4 rectum, 1 urethral).

Method

A was used in 20/22 (91%) of missed cases; 21/22 (95%) were positive at a single site. SOC failed to detect 4 infections (CT = 3, NG = 1). 90% of MSM found self-taken sampling acceptable; 85% (n = 532) would be happy to take their own samples at home.

Conclusion

PS compares well with SOC. It offers the potential for significant cost savings and easier home testing. Missed infections may be due to the method of sample processing or low organism numbers.

Abstract O18.2 Table 1Infection (N = 626)NG(Prevalence 15%, N = 94)CT(Prevalence 31%, N = 191)Overall Sensitivity % (95% CI)PS: 92 (87–93)SOC:99 (97–100)Overall Sensitivity % (95% CI)PS: 96 (90–98)SOC:98 (93–99)Method A%(95% CI%)N = 460PS: 90(82–93)SOC:99(96–100)Method A %(95% CI%)N = 460PS: 94 (86–98)SOC:97 (90–99)Method B % (95% CI%)N = 166PS: 96(87–99)SOC:100(93–100)Method B % (95% CI%)N = 166PS: 100(87–100)SOC:100(87–100)
O18.3 Utility of Cerebrospinal Fluid Analysis in the Investigation and Treatment of Neurosyphilis
Authors: Noy M L , Rayment M , Sullivan A , Nelson M
Published: July 2013

Background

British guidelines detail indications for, and interpretation of, cerebrospinal fluid (CSF) examination in those diagnosed serologically with syphilis. We wished to evaluate our current clinical practise.

Methods

We retrospectively studied all consecutive CSF syphilis tests performed in a large centre in London, UK, over five years. Indications for the examination, patient demographics, HIV metrics, serological tests for syphilis, and treatment regimens were examined.

Results

A total of 291 CSF syphilis investigations were reviewed. 19% (n = 54) were requested to confirm or refute a diagnosis of neurosyphilis. Indications included serological diagnosis of syphilis plus symptoms: headache (28%), neurocognitive decline (9%), ophthalmological symptoms (18%), hearing loss (9%), other cranial nerve involvement (6%), psychosis (4%), and treatment failure (6%).

Of this group, 37% (n = 20) were treated for neurosyphilis. 2% of those having had CSF examination for other indications were also treated for neurosyphilis (n = 5). All bar one patient were seropositive for syphilis.

Of those treated for neurosyphilis (n = 25), all were HIV positive and 88% were male. Breakdown of CSF analysis revealed: CSF syphilis enzyme immunoassay (EIA) +/VDRL+ in 4%; EIA+/VDRL- in 56%; EIA-/VDRL- in 20%; and EIA equivocal/VDRL- in 20%.

All patients in this group were treated in line with British guidelines.

Of the 34 cases not treated for neurosyphilis, results were: EIA+/VDRL- in 35%; and EIA-/VDRL- in the remainder.

No patient had a positive CSF VDRL in the absence of a negative CSF EIA.

Conclusion

All patients with a positive VDRL in the CSF were treated for neurosyphilis, but this was a rare finding; 54% of patients who were CSF EIA+/VDRL- were treated for neurosyphilis. A proportion were treated for neurosyphilis despite CSF analysis refuting the diagnosis (EIA-). Cell counts, CSF chemistry, and clinical criteria may influence these differences. Further diagnostics may improve the sensitivity and specificity of CSF examination for neurosyphilis.
O18.4 Lack of Vital Capacity of Chlamydia Trachomatis in Fallopian Tubes of Patients with Ectopic Pregnancy
Authors: Dubrovina S
Published: July 2013

Ectopic pregnancy has been serologically associated with C. trachomatis in many studies but the role of persistent chlamydial infection of the Fallopian tubes in ectopic pregnancy is still unsolved. Fresh frozen tubal and cervical tissue from 121 patients with ectopic pregnancy in a hospital setting were examined for the presence of C.trachomatis, Mycoplasma hominis/genitalium, Ureaplasma urealyticum, Neisseria spp. (including N. gonorrhoeae) and Trichomonas vaginalis DNA by polymerase chain reaction (PCR). Blood samples were analysed for antibodies to C. trachomatis (immunoglobulin (Ig) G, M and A, IgG antibodies to Chlamydia heat shock protein 60 (cHSP60) and Major Outer Membrane Protein (MOMP) and Pgp3.

Results

U. urealyticum (UU) was the most common pathogen (22.31% in tubal tissue and 27.27% in cervix) while M. hominis was a more rare agent (4.96% in tubal tissue and 4.13% in cervix) and other agents were detected even more rarely (2.48% genitalium in tubal tissue and 0% in cervix, Neisseria spp. 2.48% in tubal tissue and 5.79% in cervix, C. trachomatis 4.96% in tubal tissue and 0% in cervix, Tr. vaginalis 2.48% in tubal tissue and cervix). In most cases (73.55%) tubal pathology was associated with presence of serum G antibodies against the Chlamydial major outer membrane protein (MOMP) and Pgp3.

Conclusions

In 83.47% cases we found different kind of Chlamydial antibodies. Persistent Chlamydial infection could not be widely demonstrated in tubal tissue from these patients and the infection had probably resolved prior to the ectopic pregnancy. We believe that our negative results in PCR reflect a true absence of C. trachomatis and suggest that persistent infection of C. trachomatis in the Fallopian tubes is rare in ectopic pregnancy in our population. UU was more frequently found in both points, without a significant difference between cervical and tubal tissue, indicating that UU is a commensal microrganism.
O18.5 False Negative HSV IgG1 and IgG2 Antibody Responses in Individuals with a Recurrent Genital Herpes Infection
Authors: Roest W , Rooijen M van , Kwa D , Jansen G , Vries H de
Published: July 2013

Introduction

HSV type specific antibodies (IgG1 and IgG2) are produced and persist after HSV-1 and –2 infections. Therefore, IgG2 HSV serologic tests are used as an indicator for genital herpes history (e.g. in pregnant women), to counsel partners of genital herpes patients, and as a proxy marker of high-risk sexual behaviour. We tested this paradigm by retrospectively measuring IgG1 or IgG2 HSV antibodies in sequential serum samples from visitors with symptomatic PCR proven recurring genital herpes episodes.

Methods

We selected individuals with two episodes of PCR proven HSV-1 or HSV-2 genital herpes, which were at least 3 months apart. Serum samples collected during the second (recurring) episode were tested with a HSV type specific ELISA and Immunoblot (both Focus HerpeSelect®) for anti-gG1 or anti-gG2 antibodies. The immunoblot was used as a reference test.

Results

From May 2006 to December 2010 we selected 18 and 35 individuals with recurrent HSV-1 or HSV-2 genital herpes, respectively. In the HSV-1 cohort, serum sample testing showed that 13 out of 18 (72%) samples were tested positive in both tests, 2 out of 18 (11%) samples were positive in the gG1 ELISA but negative in the immunoblot, and 3 out of 18 (17%) samples were negative/equivocal in both tests. In the HSV-2 cohort, serum sample testing showed that 29 out of 35 (83%) samples were positive in both tests, 1 out of 35 (3%) was positive in the gG2 ELISA but negative in the immunoblot, and 5 out of 35 (14%) samples were negative in both tests.

Discussion

Our data show that HSV IgG1 and IgG2 antibodies are false negative in respectively 28% and 17% of recurrent genital infections. This should be taken in consideration when these tests are used in a clinical setting or as proxy for risk behaviour in epidemiologic studies.
O19.1 Azithromycin and Doxycycline Resistance Profiles ofMycoplasma Genitaliumand Association with Treatment Outcomes
Authors: Totten P A , Jensen N L , Khosopour C M , Gillespie C W , Jensen J S , Kenny G K , Golden M R , Manhart L E
Published: July 2013

Background

Antibiotic resistance profiles of recentMycoplasma genitalium(MG) isolates have not been extensively evaluated nor correlated with treatment outcomes for NGU. Urine specimens from men with NGU enrolled in a treatment trial in Seattle, WA were used to culture MG strains and assess the association of their susceptibility to azithromycin and doxycycline with treatment outcomes.

Methods

Urines from all MG-positive (by PCR) men were co-cultured with VERO cells. MG growth was detected by an increase in genomes using an MG-specific quantitative PCR (qPCR); minimum inhibitory concentrations (MICs) were defined by the antibiotic concentration that resulted in 99% growth inhibition. MICs were measured at baseline (V1), 3-week (V2) and 6-week follow-up (V3). Clinical cure (V2, V3) was defined < 5 PMNs/HPF, no urethral discharge or symptoms; microbiologic cure was defined by a negative MG-specific PCR result.

Results

Viable MG strains were recovered from 141 (92%) of 153 MG PCR-positive specimens; MICs were determined on 103 isolates. Azithromycin MICs were clearly bimodal; 46% (48/103) were ≤ 0.001–0.5 μg/ml, considered susceptible, and 54% (55/103) were ≥ 8 μg/ml considered resistant. Except for two strains with MICs of ≥ 8 μg/ml doxycycline, MICs were < 0.125–2 μg/ml. Doxycycline MICs did not correlate with treatment outcomes. At baseline, 33/57 (57.9%) of isolates had azithromycin MICs that were resistant. Of men in the azithromycin arm with MIC data and treatment outcomes at V2, 11/13 clinical failures (84.6%) and 16/20 microbiologic failures (80.0%) had azithromycin resistant isolates at baseline. After receiving azithromycin, 9/10 V2 clinical failures (90%) and 12/13 microbiologic failures (92.3%) had V2 azithromycin resistant MICs. All V3 clinical (7/7) and microbiologic (10/10) failures had V3 azithromycin resistant MICs.

Conclusion

Approximately 60% of MG strains were resistant to azithromycin at baseline; azithromycin treatment failures occurred in 90–100% of men who received azithromycin. Development of new antimicrobial therapies for MG is essential.
O19.2 Mycoplasma Genitalium is as Frequent a Cause of Urethritis as Chlamydia Trachomatis, and Has High Rates of Genotypic Resistance to Macrolide Antibiotics
Authors: Pond M J , Nori A , Witney A A , Lopeman R , Butcher P D , Sadiq S T
Published: July 2013

Background

When choosing empirical anti-microbial therapy for non-gonococcal urethritis (NGU) and cervicitis, efficacy against Chlamydia trachomatis over Mycoplasma genitalium is prioritised. However, M.genitalium is associated with reproductive sequelae in women and first-line recommended therapy with macrolide antibiotics differs to that for Chlamydia infection. We determined: M.genitalium and C.trachomatis frequency among symptomatic men with and without urethritis; prevalence of macrolide and fluoroquinolone associated genotypic resistance in M.genitalium; and the phylogenetic spread of genotypic M.genitalium antimicrobial resistance using a validated dual-locus typing system.

Methods

Urethritis was diagnosed by combining urethral smear and clinical criteria. Nucleic acid amplification was used for detecting M.genitalium and C.trachomatis. Single nucleotide polymorphisms (SNPs) in the 23S ribosomal RNA gene (23S rRNA), in gyrA, gyrB, and parC were detected by DNA sequencing. MG191 SNP typing and MG309 variable number tandem analysis were utilised to assess M.genitalium strain diversity.

Results

217 men were recruited. C.trachomatis and M.genitalium prevalence was 14.7% (95% CI: 7.8–21.6) and 16.7% (95% CI: 9.5–24.0) respectively in NGU cases and both significantly higher than in those with no urethritis. 9/22 (41%; 95% CI: 20%–62%) of M.genitalium strains had markers of macrolide associated genotypic resistance. Of 15 M.genitalium strains analysed only one possessed a parC mutation, associated with fluoroquinolone resistance. Dual-locus typing assigned all M.genitalium strains to two major clusters, both of which contained diverse strains carrying resistant mutations. All strains were phylogenetically dispersed among international reference controls, typed using MG191.

Conclusion

Frequency of M.genitalium was as high as C.trachomatis in NGU patients. More than 40% of M.genitalium strains had SNPs associated with macrolide resistance but fluoroquinolone associated genotypic resistance was rare. All strains were phylogenetically dispersed indicating that these infections were probably not part of a local clonal expansion. Treatment guidelines for NGU require re-appraisal in light of these findings.
O19.3 Estimate of the Prevalence of Transmitted Drug Resistance (TDR) and Acquired Drug Resistance (ADR) in a HIV Resistance Study of the German ClinSurv-HIV Cohort
Authors: Bartmeyer B , Schmidt D , Kollan C , Fätkenheuer G , Stellbrink H , Bogner J , Jensen B O , Stoll M , Kücherer C , Hamouda O
Published: July 2013

Aim

To estimate the prevalence of HIV-TDR and ADR in one resistance study of the German ClinSurv-HIV cohort.

Method

The ClinSurv study is a national open multi-centre long term observational cohort with 15 participating clinical centres (n = 16,750 patients; 31.12.2011). In a resistance study all ClinSurv patients in five centres were identified. Sequences were processed through the Stanford University Genotypic Resistance Interpretation Algorithm (www. hivdb.stanford.edu;HIVdb version 6.1.1F; 2012 webService version beta-1.0.1) to identify mutations and to determine drug susceptibility. Sequences were analysed by using different lists of mutations (Bennett D. 2009; Johnson V. 2011). Trends in the prevalence of drug resistance mutations were calculated by logistic regression.

Results

A total of 9,528 patients from five study centres were included into analysis. 4,989 viral sequences were collected from 34% (3,267/9,528) of these patients. 47% (2,365/4,989) of sequences were produced from patients being treatment naïve and 50% (2,495/4,989) from patients under treatment. TDR was identified in 10% (203/1,950) of viral strains. The prevalence of TDR over time was stable at 10.4% (95% CI 9.1–11.8; OR: 0.98; 95% CI 0.92–1.04; pfor trend= 0.6; 2001–2011). NRTI-resistance was determined in 7% (128/1,950), followed by 3% NNRTI- and PI-resistance, respectively (NNRTI: 61/1,950; PI: 56/1,950). Prevalence of ADR in treated patients was high (61%; 1,500/2,453 of sequences) but declined significantly over time (OR: 0.8; 95% CI 0.77–0.83; pfor trend< 0.001; 2001–2011). Within drug classes NNRTI-resistance was predominant (56%; 834/1503), followed by NRTI-resistance in 52% (1,139/2,194) of sequences of patients with ADR exposed to these drug classes. PI-resistance was identified in 30% (543/1778). Integrase-resistance was determined in 8% (13/161) of integrase-sequences.

Discussion

Prevalence of TDR is highly stable in this unselected study population, whereas ADR declined significantly over the time, indicating that this decline was presumably influenced by ART related effects, broader resistance testing and resistance test guided therapy.
O19.4 Acceptability of HPV Vaccination Among Parents of Adolescent School Going Girls in Mysore City, India
Authors: Krupp K , Srinivas V , Marlow L , Li T , Albetini A , Gowda S , Arun A , Jaykrishna P , Madhivanan P
Published: July 2013

Background

One in every four reported cases of cervical cancer occurs in India. While mortality from the disease has all but disappeared in industrial countries, 74,000 Indian women still die each year from this preventable cancer. It has been estimated that widespread uptake of HPV vaccine by adolescent girls could reduce this high incidence and mortality by approximately two-thirds. This study explores correlates of HPV vaccine acceptability among parents of adolescent school-going girls in urban Mysore, India.

Methods

Between August and December of 2011, participants were selected by stratified, multi-stage random sampling in schools located in Urban Mysore. Questionnaires were sent home with a random sample of 800 adolescent girls 11–15 years of age attending 10 schools in Mysore city to be completed by a parent. Logistic regression was used to assess factors associated with parental acceptability of HPV vaccine.

Results

797 completed surveys (99.6%) were received back from parents. About 72% of respondents would accept the HPV vaccine for their daughters. Vaccine acceptance was higher among participants who had experienced cancer in their family (OR: 1.69, 95% CI: 1.07, 2.65), or perceived that their family doctor (5.04; CI 3.27, 7.76) or spouse (5.01; CI: 3.20, 7.87) would approve. Parents having concerns about vaccinations in general (0.38; CI: 0.25, 0.57), vaccine side-effects (0.65; CI: 0.45, 0.94), vaccine safety (0.64; CI: 0.42, 0.97) or the possibility that their daughter might become sexually active (0.71; CI: 0.28, 0.76) had lower odds of accepting HPV vaccination. Parents belonging to the Muslim religion (0.54; CI: 0.37, 0.80) had lower odds of vaccine of HPV vaccine acceptance.

Conclusion

The majority of parents of school-going adolescent girls in Mysore found HPV immunisation acceptable. Further research is needed to understand the issues associated with HPV vaccination in different religious groups in India.