bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

BackgroundOf 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.MethodsBased 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).ResultsThere 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.ConclusionAll 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

BackgroundThe 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.MethodsThe 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.ResultsFrom 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).ConclusionDespite 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

IntroductionThe 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.MethodsSerial 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.ResultsThe 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.ConclusionsThe 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

BackgroundAPTIMA 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).MethodsMSM (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).Results627/700 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).MethodA 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.ConclusionPS 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

BackgroundBritish 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.MethodsWe 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.ResultsA 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.ConclusionAll 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.ResultsU. 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.ConclusionsIn 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

IntroductionHSV 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.MethodsWe 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.ResultsFrom 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.DiscussionOur 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

BackgroundAntibiotic 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.MethodsUrines 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.ResultsViable 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.ConclusionApproximately 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

BackgroundWhen 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.MethodsUrethritis 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.Results217 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.ConclusionFrequency 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

AimTo estimate the prevalence of HIV-TDR and ADR in one resistance study of the German ClinSurv-HIV cohort.MethodThe 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.ResultsA 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.DiscussionPrevalence 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.