bluuebunny/crossref_metadata_2025 huggingface dataset:
O3-S2.03 The spectrum of genital HPV infection among men attending a Swedish STI Clinic: HPV typing and clinical presentation
Authors: Wikström A , Hedblad M A , Syrjänen S
Published: July 2011

Background

Some Swedish studies on HPV typing in men exist. Most earlier studies have used less sensitive HPV typing techniques. The purpose of this study is to see if the HPV types in genital HPV associated lesions have changed since the 80ies, and to describe the lesions in detail.

Methods

Between 2004 and 2007, male patients attending the STI clinic of Karolinska Hospital with genital HPV induced lesions planned for surgery, were asked to participate in the study. All men exhibited multiple lesions—men with solitary lesions were excluded. Two clinically identical lesions on the same genital site, were collected by punch biopsy or by scissor excision. One sample was put in formalin for histopathological routine preparation, and the other sample was frozen in −70°C for PCR analysis using a highly sensitive nested PCR technique, detecting 24 different HPV types. The macroscopic morphology of the lesions was classified in acuminate, papular, macular and seborrhoeic keratosis like. The colour of the lesions and the location were recorded. Data on previous therapy and how long time the patients had been afflicted with genital symptoms/and or warts was also noted.

Results

Totally 303 men were included in the study. Of these, 47 men (16%) exhibited lesions of PIN and have been described previously. The remaining 256 men had benign lesions and are described here. Acuminate lesions dominated, occurring in 106 (41%) of the men, followed by papular lesions found in 88 (34%) men. The penile shaft, the pubic area and the foreskin were the most common locations for the HPV induced lesions, afflicted in 36%, 29% and 25% of the men, respectively. Pink and brown were the dominating colours of the leions. HPV was detected in 233 (91%) lesions. Low risk HPV types only, were found in 75% of the lesions. On the other hand, 7% of the lesions contained only high risk HPV types, and 9% had a mix of low- and high risk HPV types. Multiple HPV types were found in 13%. HPV 6 was the most common HPV type (70% of the lesions were positive for HPV 6 only). Duration of genital symptoms and/or warts was mean 24 months and 211 of the men had previously been treated.

Conclusion

Using a highly sensitive PCR technique, a high HPV detection rate of 91% was found. As in earlier studies, HPV 6 was most common, but also other HPV types including high-risk types were detected. As expected, most of the benign lesions were acuminate, but the morphology as well as the genital location varied.
O3-S2.04 Cervical ectopy is not associated with acquisition of HPV infection
Authors: Hwang L Y , Lieberman J , Ma Y , Moscicki A B
Published: July 2011

Background

HPV infection and cervical cancer are often found at the cervical transformation zone. High rates of HPV in adolescents have been attributed to their greater extent of “cervical ectopy”, defined as areas of columnar and metaplastic epithelium visible on the ectocervix. The study aim was to examine associations between the extent of cervical ectopy and incident HPV infection in healthy adolescents.

Methods

Sexually active young women were enrolled as part of a prospective HPV Natural History Study. Women were eligible if they were 13–21 years old, sexually active (5 years maximum), and had no history of cervical intraepithelial neoplasia, cervical procedures, or immunosuppression. At 4-month interval visits, we performed colpophotography to document the epithelium, HPV testing for 37 types by Roche Reverse Line Blot assay, and interviews to assess behaviours. This study selected women (N=147) who had negative HPV results at the first two consecutive visits. Epithelial areas of interest were measured in the digitised colpophotographs by using computerised planimetry to produce pixel counts. The extent of ectopy was measured as a percentage of the total cervical face. Cox proportional hazards models examined ectopy as a predictor for incident HPV, defined as the first positive HPV result following the initial two negative results, adjusted for the number of new sexual partners. Outcomes included incidence of any HPV type; α-9 HPV types (defined as 16, 31, 33, 35, 52, 58, 67); and a-3/15 HPV types (defined as 61, 71, 72, 81, 83, 84, 89).

Results

The 147 women attended a total of 545 visits. The mean age at baseline was 17.2 years, mean age of menarche was 12.8 years, and mean age of first sex was 15.4 years. Self-reported race/ethnicity was 35 (24%) Asian, 14 (10%) African-American, 43 (29%) Caucasian, 52 (35%) Latina, and 3 (2%) Other. The median ectopy measurement from the 545 visits was 14% (interquartile range 6–32%) of the total cervical face. Incident HPV of any type was found in 42 (29%) women. The extent of ectopy was not significantly associated with incidence of any HPV type (HR 1.004, p=0.63); α-9 HPV types (HR 0.99, p=0.43); or α-3/15 HPV types (HR 1.02, p=0.18). Results were unchanged when adjusted for new sexual partners in the past 8 months (HR 1.9, p<0.01).

Conclusions

When measured quantitatively, the extent of cervical ectopy is not a risk factor for the acquisition of HPV infection in healthy adolescent women.
O3-S2.05 Prevalence ofTrichomonas vaginalisand co-infection withChlamydia trachomatisandNeisseria gonorrhoeain the USA as determined by the APTIMATrichomonas vaginalisnucleic acid amplification assay
Authors: Ginocchio C C , Chapin K , Smith J S , Aslanzadeh J , Snook J , Hill C S , Gaydos C A
Published: July 2011

Background

Trichomonas vaginalis(TV) is the most common curable sexually transmitted infection worldwide. True prevalence of TV infection is not well characterised as previous studies mainly used methods with relatively poor sensitivity compared to nucleic acid amplification methods. Our aim was to determine TV prevalence using the APTIMA TV Assay (ATV, Gen-Probe Incorporated) and the frequency of co-infections withChlamydia trachomatis(CT) andNeisseria gonorrhoea(NG) in the USA among women being screened.

Methods

Samples from 7593 women aged 18–89 years undergoing routine CT and NG screening at obstetrics/gynaecology, emergency room, hospital in-patient, family practice, family planning, internal medicine, jail, and STD clinic populations in 21 states were collected. Consecutive samples previously tested for CT and NG by the APTIMA COMBO 2 Assay (Gen-Probe Incorporated) were retrospectively tested with the ATV assay. Endocervical, urine, vaginal swab and PreservCyt liquid Pap samples (Hologic Inc.) diluted into APTIMA specimen transport buffer were tested.

Results

Overall prevalences of TV, CT and NG in surveyed women were 8.7%, 6.7%, and 1.7%, respectively. TV prevalence ranged from 7.5 to 8.6% in women age 18 to 39 yr, and increased to 9.8% in women age 40–44 yr. Highest observed TV prevalences were in women ages 45–49 yr (13.4%) and over 50 yr (13.0%). CT and NG prevalences were less than 2% in the 40+ age group and highest in women less than 30 years of age ranging from 5.2% to 14.3% for CT and 1.3%–3.3% for NG. TV was the more prevalent STD than either CT or NG in all age groups, except the 18-19 yr group (CT: 14.3%; TV: 8.5%). TV prevalence differed by race/ethnicity (20.2% blacks; 5.7% whites; 5.0% Hispanics; 3.8% Asians). TV prevalence was 14.4% in the Southeast, 9.5% in the Southwest and Midwest, and 4.3% in the Northeast and ranged from 5.4% in Family Planning clinics to 22.3% in jails. Co-infections in most age groups were <1%, and were highest in the 18–19 yr group (TV/CT: 2.1%; TV/NG: 0.88%).

Conclusions

TV prevalence was highest in women over 40 years of age, in contrast to CT and NG prevalences which were highest in women under 30 years of age. Co-infection of TV with CT or NG was relatively low. The high TV prevalence in all age groups suggests that all women being screened for CT/NG should also be screened for TV. Routine TV screening should also be considered for at-risk sexually active women of any age.
O3-S3.01 Comparison of a new APTIMA specimen collection and transportation kit to L-Pap for detection ofC trachomatis,N gonorrhoeaeandT vaginalisin cervical and vaginal specimens
Authors: Chernesky M
Published: July 2011

Background

Control of sexually transmitted infections in women has focused on screening using cervical, vaginal or urine samples. The objective was to compare a new specimen collection and transportation (SCT) kit to PreservCyt (PC) and SurePath (SP) liquid-based Pap (L-Pap) for cervical sampling and self- and physician-collected vaginal samples.

Methods

Women (n=562) attending a gynaecology clinic (GYC) (n=435) or a youth health clinic (YHC) (n=127) signed consent for a physician to collect two L-Pap samples with a Cervex broom, cervical (CSCT) and vaginal (VSCT) samples and a self-collected VSCT. All specimens were tested for Chlamydia trachomatis (CT) andNeisseria gonorrhoeae(NG) by APTIMA Combo 2 (AC2) andTrichomonas vaginalis(TV) by APTIMA TV on a TIGRIS instrument. Each patient was asked on a scale of one to five to express strength of agreement or disagreement with ease or comfort of the 6 step self collection process for the VSCT.

Results

There were a total of 22 CT, 19 TV and 2 NG infections with dual infections in 6 people (one CT and NG, one NG and TV and four CT and TV). Prevalences were as follows: CT 3.9% (GYC 1.3% and YHC 12.6%); NG 0.3% (2.0% in YHC); TV 3.4% (GYC 0.4% and YHC 13.4%). Sensitivity for CT infections were CSCT 100%, PC 100%, SP 81.8%; VSCT-self 100%, VSCT-physician 95.4%: for TV infections CSCT 89.4%, PC 84.2%, SP 63.2%; both VSCT 100%: for NG all collections 100%. There were no false positives (% specificity 100). Results of the survey revealed that the majority of patients found opening the package, self sampling, insertion of the SCT swab into preservation media and uncapping and recapping the tube were relatively easy to perform. Eighty two per cent experienced no discomfort using the SCT kit for collection.

Conclusions

APTIMA testing on the TIGRIS showed that the cervical and vaginal SCT and PC L-Pap samples were 100% sensitive in detecting CT and NG infections. VSCT samples detected all TV infections but cervical SCT and PC L-Pap were less sensitive. SP L-Pap samples showed reduced sensitivity for CT and TV. Overall, patients were in strong agreement with the ease of use of the VSCT and most found the process comfortable.
O3-S3.03 DifferingNeisseria gonorrhoeaebacterial loads in the pharynx and rectum: implications for gonococcal detection, transmission and control
Authors: Bissessor M , Tabrizi S , Fairley C , Danielewski J , Whitton B , Bird S , Garland S , Chen M
Published: July 2011

Background

To help improve our understanding of the potential transmissibility of gonococcal infections from the pharynx and rectum we measured gonococcal bacterial loads at these sites and examined clinical and laboratory determinants of these loads.

Methods

Men who had sex with men were tested for pharyngeal and rectal gonorrhoea by culture using modified Thayer Martin medium and by two real-time quantitative qPCRs targetting opa gene, and porA pseudogene.

Results

1011 rectal and 1076 pharyngeal specimens were obtained from 1076 MSM. Forty three (3.9%) pharyngeal specimens were PCR positive of which 17 were culture positive (sensitivity 39%, 95% CI: 25% to 54%). Forty seven (4.6%) rectal specimens were PCR positive of which 25 were also culture positive (sensitivity 58%, 95% CI 44% to 71%). The median bacterial load among PCR positive rectal infections (18 960 copies per swab) was significantly higher than that for PCR positive pharyngeal infections (2,100 copies per swab) (p=0.001). The median bacterial load among men with symptomatic rectal infection was higher (278 800 copies per swab) than with asymptomatic men, PCR positive rectal infections (13,980 copies per swab, p<0.001). The median bacterial load of gonorrhoea was significantly higher in culture positive than culture negative specimens. This applied for both rectal (p<0.001) as well as pharyngeal infections (p=0.03).

Conclusion

Higher bacterial loads of gonorrhoea were observed in rectal infections, particularly with symptomatic rectal infections. This has implications for gonococcal transmission and control.
O3-S4.01 The new superbugNeisseria gonorrhoeaemakes gonorrhoea untreatable?—first high-level ceftriaxone resistance worldwide and public health importance
Authors: Ohnishi M , Unemo M , Golparian D , Shimuta K , Saika T , Hoshina S , Iwasaku K , Nakayama S I , Kitawaki J
Published: July 2011

Background

The firstNeisseria gonorrhoeaestrain (H041) worldwide that is highly resistant to the extended-spectrum cephalosporin (ESC) ceftriaxone, which is the last remaining option for empirical treatment of gonorrhoea, has now been identified! This is a large public health problem and the era of untreatable gonorrhoea may now have been initiated. The present study completely characterised H041, phenotypically and genetically, to confirm the finding, comprehensively examine its antimicrobial resistance (AMR) and in detail elucidate the resistance mechanisms. Finally, public health actions for preventing and/or detaining global spread of ceftriaxone-resistant and untreatable gonorrhoea will be discussed.

Methods

H041 was examined using seven species-confirmatory tests, antibiograms (30 antimicrobials) with Etest and agar dilution (only for ESCs), porB sequencing,N gonorrhoeaemulti-antigen sequence typing (NG-MAST), multilocus sequence typing (MLST) and sequencing of ESC resistance determinants (penA, mtrR, penB, ponA and pilQ). Transformation, using appropriate recipient strains, was performed to confirm the ESC resistance determinants.

Results

H041 was assigned serovar Bpyust, MLST ST7363 and the new NG-MAST ST4220. H041 proved highly resistant to ceftriaxone (2–4 mg/l, which is 4-8-fold higher than any previously described isolate) and all other cephalosporins, as well as most other antimicrobials tested. A new penA mosaic allele, containing only four not previously described amino acid alterations, caused the ceftriaxone resistance, which was all proven using several transformation experiments.

Conclusions

The new superbugN gonorrhoeaehas now developed also ceftriaxone resistance and an era of untreatable gonorrhoea may have been initiated. A reduction in global gonorrhoea burden by enhanced disease control activities combined with wider strategies for general AMR control and enhanced understanding of mechanisms of emergence and spread of AMR, which need to be monitored globally, is crucial. Furthermore, a public health response plan (including sustainable clinical, microbiological and epidemiological components) for a global perspective is essential. Ultimately, new drugs are essential to develop for efficacious gonorrhoea treatment.
O3-S4.03 Safety and efficacy of WC2031 vs vibramycin for the treatment of uncomplicated urogenitalChlamydia trachomatisinfection
Authors: Geisler W M , Mena L , Taylor S N , Batteiger B E , Thurman A , Hook E W , Koltun W D , Abdelsayed N , Vaughn T A , Annett M P ,   WC2031 Investigator Team
Published: July 2011

Background

Recent studies report that treatment failure rates for single-dose azithromycin for urogenital chlamydia in females may be as high as 8%. There has been sparse research investigating new antibiotics for chlamydia, especially those that may reduce adherence difficulties with the CDC recommended doxycycline regimen (100 mg orally twice daily for 7 days).

Methods

The safety and efficacy of WC2031 (doxycycline hyclate delayed-release 200 mg tablet) orally once daily for 7 days vs Vibramycin (doxycycline hyclate capsule) 100 mg orally twice daily for 7 days for the treatment of uncomplicated urogenital chlamydia was evaluated in a randomised, double-blind, double-dummy, active-controlled, multicenter study. Males and nonpregnant females ages 19–45 with a confirmed diagnosis of urogenital chlamydia <14 days prior to enrolment or with a sexual partner with chlamydia were eligible. The study consisted of three visits: baseline, day 8 (end-of-treatment), and day 28 (test-of-cure [TOC]). The primary outcome was microbiological cure at TOC, defined as a negative result for Chlamydia trachomatis by the Gen-Probe (GP) Aptima Combo (AC) 2 assay (on urine in males and vaginal swab in females). The mITT population consisted of treated subjects with a GP AC2 positive forC trachomatisat baseline. Non-inferiority of WC2031 was inferred if the lower limit of the 95% CI of the difference in cure rates was >-10%. Safety was studied through clinical evaluation and laboratory tests.

Results

495 subjects were randomised at 41 study sites. The mITT population with evaluable efficacy consisted of 323 (65%) subjects (156 in the WC 2031 group and 167 in the Vibramycin group). Baseline characteristics did not differ by group: median age 23, 61% female, 58% African American vs 36% Caucasian vs 7% other race, and 21% Hispanic ethnicity. The microbiological cure rate (95% CI) for the WC2031 group was 95.5 % (92.3 to 98.8) vs 95.2% (92.0 to 98.4) for the Vibramycin group; the 95% CI for the difference in cure rates between treatments was (−4.3% to 4.9%). Types of adverse events were comparable between treatment groups. The WC 2031 group had less nausea and vomiting (13% vs 21% and 8% vs 12%).

Conclusions

WC2031 was non-inferior to Vibramycin for treatment of uncomplicated urogenital chlamydia, was better tolerated, and demonstrated comparable safety. The once daily dosing of WC2031 may improve treatment adherence compared with twice daily doxycycline.
O3-S4.05 Treatment of students infected with chlamydia and gonorrhoea in a school-wide screening program
Authors: Taylor S N , Brennan C , Longfellow L , Martin D H , Nsuami M J
Published: July 2011

Background

Providing treatment to individuals screened for a health condition is a key component of any health screening program. School-based screenings for sexually transmitted diseases (STD) offer the possibility of efficiently and promptly treating participants because students can be easily located after they have been tested. We describe treatment rates and time to treatment for students with Chlamydia trachomatis (CT) orNeisseria gonorrhoeae(NG) infection in a school-wide screening program.

Methods

Between 1995 and 2005, 20 224 high school students were tested for CT and NG during annual screenings using urine specimens and commercial nucleic acid amplification tests. Test results were available approximately five working days after specimen collection. Students who tested positive were located at school during regular class hours for counselling and treatment by a school nurse, a clinic nurse, a public health nurse, or a physician. Treatment was with a single 1 gram oral dose of azithromycin for CT and 500 mg oral ciprofloxacin for NG, administered under direct observation. Before its removal from the market, cefixime 400 mg in single oral dose was used to treat NG. The names of infected students who could not be located in school were forwarded to a public health Disease Intervention Specialist (DIS) for follow-up. The DIS provided the program with an update on the follow-up status of each name referred.

Results

During the 10-year period, 3422 infections (CT: 2746; NG: 304; CT and NG: 372) were identified. Treatment was documented for 2844 infections (83.1%). There were no significant differences in rates of treatment (p>0.37) by gender or by infection. The rates of treatment varied by school year from a low of 64.8% in 1996–1997 to a high of 94.9% in 1997–1998 (p<0.0001). For 2692 infections with documented dates of treatment, the median time from specimen collection to treatment was 21 days (75th percentile: 33 days).

Conclusions

This high school STD screening and treatment program achieved high treatment rates for both CT and NG, although the treatment effort required strong commitments of various individuals from the screening program, the administrations in participating schools, and the local health services. Differences in treatment rates per school year reflected the dynamic interplay of these various individuals and organisations as well as the commonly high absentee, truancy, and dropout rates among students in the school district.
O3-S5.05 RPR titre variation following early syphilis therapy: a potential confounder of treatment outcome assessment
Authors: Holman K , Wolff M , Seña A , Martin D , Behets F , Van Damme K , Leone P , McNeil L , Winestone J , Hook E
Published: July 2011

Objective

Serologic tests for syphilis (STS) results at the time of diagnosis are the basis for evaluating response to syphilis therapy. Following treatment, however, STS titres may continue to increase for several weeks. In a recent study comparing azithromycin to penicillin or doxycycline for early syphilis treatment, patients had RPR titres measured initially, at 7 and at 14 days following treatment. We evaluated variation in RPR titres over the 14 days following therapy, hypothesising that RPR titre changes would vary with stage and initial titre.

Methods

Prospectively identified HIV-seronegative participants at five North American and three Madagascar sites with primary, secondary or early latent syphilis were randomly assigned to penicillin, doxycycline (in the case of penicillin allergy) or azithromycin treatment. Blood for RPR analysis was drawn at days 0, 7, and 14 post-treatment. All RPR titres were determined simultaneously at a central laboratory. Analysis was done using SAS 9.2.

Results

465 patients had data available for at least 2 of 3 RPR measurements. Median RPR at diagnosis by stage was Primary 1:16, Secondary 1:64, Early Latent 1:32. Overall, 20% of patients showed a titre increase of at least one dilution in the 14 days following therapy. Of this group, 88.2% demonstrated an increase of 1 dilution, while 11.8% demonstrated an increase of ≥2 dilutions. The greatest proportion of titre increases following therapy was seen in patients with primary syphilis.

Conclusions

Given the reliance upon changes in RPR titres for evaluating response to therapy, these changes in titre following therapy could affect whether a response is classified as treatment success/failure or serofast status. Further analyses will evaluate factors associated with increasing RPR titres following therapy, as well as the effect of these changes in titre on evaluation of response to therapy.

Abstract O3-S5.05 Table 1StageNMedian RPR at diagnosis% With increased titres within 14 days following treatment (95% CI)% With titres increased by one dilution following therapy (95% CI)% With titres increased by ≥2 dilutions following therapy (95% CI)Primary1151:1630.4 (22.2 to 39.7)80.0 (63.1 to 91.6)20.0 (8.4 to 36.9)Secondary2181:6417.0 (12.2 to 22.6)97.3 (85.8 to 99.9)2.70 (0.1 to 14.2)Early latent1321:3215.9 (10.1 to 23.3)85.7 (63.7 to 97.0)14.3 (3.0 to 36.3)Total4651:6420.0 (16.5 to 23.9)88.2 (79.8 to 93.9)11.8 (6.1 to 20.2)
O3-S5.06 Double-blind randomised placebo controlled trial of oral metronidazole in combination with either vaginal clindamycin or an oestrogen-containing vaginal probiotic for the treatment of bacterial vaginosis
Authors: Bradshaw C , Pirotta M , Hocking J , Garland S , de Guigand D , Fehler G , Morrow A , Walker S , Vodstrcil L , Fairley C
Published: July 2011

Background

To determine if addition of vaginal clindamycin or an oestrogen-containing vaginal probiotic, to current recommended therapy for bacterial vaginosis (BV), oral metronidazole for 7 days, reduces 6 month recurrence rates.

Methods

Three arm randomised double-blind placebo controlled trial of 450 women (150 per arm): [MetPlac] oral metronidazole (7 days)/vaginal placebo (12 days), [MProb] oral metronidazole (7 days)/vaginal probiotic(12 days) and [MetClin] oral metronidazole (7 days)/vaginal clindamycin (1 g 2% nocte,7 days). Symptomatic 18–50-year-old females with BV on vaginal swab by the Nugent method were enrolled at Melbourne Sexual Health Centre, Australia. Participants underwent initial examination & STI screen and completed a detailed behavioural questionnaire at 0, 1, 2, 3 & 6 months. At each interval participants were posted a kit containing swabs and a slide for self-collection and a questionnaire. Principle study outcome: Nugent score of 7–10. Cumulative BV recurrence rates were calculated and compared using χ2and survival analyses using SPSS and STATA.

Results

450 women with BV were recruited from December 2007 to May 2010. Median age was 27 years (range 18–49), 210 (48%) reported a past history of BV; there were no significant differences in participant demographic or behavioural characteristics between arms. Adherence to study medication did not differ between arms: 382 (91%) took all or most oral metronidazole and 330 (80%) all or most vaginal therapy. Retention rates were high, with 77 (17%) lost to follow-up over 6 months, and did not differ between arms. Participants contributed 153.7 person years of follow-up to analyses. On exit survey 88% of participants did not know or correctly guess the vaginal therapy they had received. Six month cumulative BV recurrence rates did not differ between study arms by per protocol analysis: MetPlac (32%, 95% CI 24% to 41%) MetProb (33%, 25% to 42%) and MetClin (34%, 26% to 42%), p>0.05 (Abstract O3-S5.06 figure 1), or intention-to-treat analysis (noncompleter=recurrence) [recurrence range 44-9%].

Abstract O3-S5.06 Figure 1

Conclusions

The addition of vaginal clindamycin or a vaginal probiotic to oral metronidazole does not improve 6 month BV recurrence rates. This is the first RCT to evaluate the efficacy of combination clindamycin/metronidazole for BV treatment, and has important implications for clinical practice. Combination therapy is often used in patients with recurrent BV, but evidence to support this practice has not been available.
O3-S6.04 Multi-site screening for lymphogranuloma venereum (LGV) in the USA
Authors: Hardick J , Quinn N , Eshelman S , Piwowar-Manning E , Cummings V , Marsiglia V C , Gaydos C A ,   The HPTN 061 Study Team
Published: July 2011

Background

Lymphogranuloma venereum is a clinical condition caused by infection with one of theChlamydia trachomatis(CT) L serovars. Proper diagnosis of LGV is critical as the treatment varies significantly from antibiotic therapy utilised for other CT infections. LGV has re-emerged in Europe as an important sexually transmitted infection (STI), particularly in men who have sex with men (MSM), due to an outbreak in the Netherlands. LGV surveillance data for the USA is lacking as LGV screening is not routinely performed, even in high risk populations. This study presents LGV surveillance data from multiple sites in the USA.

Methods

1671 rectal samples from African-American MSM participating in a study of the HIV Prevention Trials Network (HPTN 061) BROTHERS Project, were collected from six different cities: Los Angeles and San Francisco CA, Atlanta, GA, Boston MA, Washington D.C., New York, NY; and tested for CT by Aptima Combo 2 (Gen-Probe). Additionally, 127 samples from men from Baltimore, MD who reported anal sex or were symptomatic for CT, and had rectal swabs positive for CT by Combo 2 were also included. All samples were screened for LGV utilising a previously verified LGV specific real-time PCR to determine if the samples were positive for any one of the CT L serovars.

Results

Of the 1671 HPTN 061 samples, 112 (6.75%) were positive for CT and 102 of these have been screened thus far for LGV; none were LGV+. Of 127 CT+ samples from Baltimore, two were LGV+. Thus, of 229 CT+ rectal samples, only 2 (0.87%), tested positive for LGV by real-time PCR.

Conclusions

Less than 1% of the CT positive samples obtained from rectal swabs from MSM in the US tested positive for LGV. The samples utilised for this study were from a population presumably at high risk for acquisition of LGV, as all samples tested were from men who had either tested positive for CT, reported anal sex, or were symptomatic for CT infection. The prevalence for LGV in this study was quite low, while the non LGV CT prevalence was high in African American MSM from the six cities. Concomitant STDs are thought to drive the disproportionate HIV epidemic among African American MSM and the low prevalence of LGV in this study is of interest. LGV has re-emerged as an important STI in Europe, however this data suggests that it has either not re-emerged in the U.S. or has re-emerged in a population that is not being screened.
O3-S6.05 Perceptions on point-of-care tests for sexually transmitted infections‑disconnect between frontline clinicians and professionals in industry
Authors: Hsieh Yu-Hsiang , Gaydos C , Hogan T , Uy O , Jackman J , Jett-Goheen Mary , Rompalo A
Published: July 2011

Background

Some recently developed or available sexually transmitted infection (STI) point-of-care tests (POCTs) are not very accurate and are not feasible for use in clinical settings. We conducted a study to determine if a gap exists between STI clinicians/academic experts and industry professionals regarding perceptions of the ideal types and characteristics of STI POCTs.

Methods

Our online survey design informed by a large-scale focus group study among STI professionals contained sections on demographics; barriers of use for available STI POCTs; characteristics of an ideal POCT, including prioritising pathogens for targets; and building your own POCT". Practicing clinicians and academic experts from two venues, STI-related international conference attendees and U.S. STD clinic clinicians, were invited to participate in the clinician survey. Professionals from industry in the STI diagnostic field were invited to participate in the industry survey. χ2test and conditional logistical regression were used for data analysis.

Results

Clinician survey participants (n=218) identified “the time frame required” (39.9%), “complexity” (31.2%), and “interruption of work flow” (30.3%) as the top three barriers making it difficult to use STI POCTs, while the industry survey participants (n=107) identified "complexity" (65.4%), “unreliability” (53.3%), and “difficulty in reading results” (34.6%) as the top three barriers. Significant differences in barriers named in the two surveys included “complexity”, “the time frame required”, “laboratory driven”, “difficulty in reading results”, and “unreliability”. Participants from both surveys rankedC trachomatisas the top priority organism chosen for a new POCT (clinician: 62%, industry: 39%, p<0.05), followed by a test that would diagnose early seroconversion for HIV (clinician: 14%, industry: 32%, p<0.05). Sensitivity was always the most important attribute to be considered for a new STI POCT by both participant groups. Participants of the clinician group chose cost as the second priority attribute, while those of the industry group chose specificity as the second priority.

Conclusions

We identified differences in the perceptions regarding barriers and ideal attributes for STI POCTs between frontline clinical providers and industry personnel. Tailored training is warranted to inform scientists, biomedical engineers, and other industry experts about characteristics that clinicians desire for STI POCTs.
O4-S1.01 Rapid array-based multilocus genotyping ofChlamydia trachomatis: the easy and economical alternative
Authors: Herrmann B , Christerson L , Ruettger A , Gravningen K , Ehricht R , Sachse K
Published: July 2011

Background

Genotyping ofChlamydia trachomatis(C.) is an important technique to understand its epidemiology. Methods such as DNA sequencing of the ompA gene or multilocus sequence typing (MLST), either offer limited epidemiological resolution, or are laborious and expensive, or both. Here we present a microarray-based method for genotyping ofC trachomatis.

Methods

The database for our high-resolution MLST system (http://mlstdb.bmc.uu.se/) was used to design a multilocus typing (MLT) DNA microarray based on the ArrayStrip format (Alere Technologies, Jena, Germany). In total, the present MLT array version includes 210 different oligonucleotide probes covering the discriminatory variation in the highly variable, but stable, MLST target regions (hctB, CT058, CT144, CT172 and pbpB), as well as 61 probes for ompA. Validation of the array was done by examining 80 clinical C. trachomtis specimens from unselected adolescents and compare with results from MLST and ompA-based serotyping.

Results

Successful typing was achieved for 78 (97%) of the specimens. Processing of the obtained hybridisation patterns resulted in 17 different MLT array groups, whereas sequence-based examination led to 19 MLST genotypes and seven ompA genotypes. Thus, the MLT microarray assay provided 2.4 times higher resolution than ompA and separated the commonly predominating ompA E/Bour genotype into seven genotypes. The MLT array showed 100% specificity. Compared to MLST analysis, the equipment needed for the MLT array is about 75% cheaper, consumables are 50% cheaper, analysis can be completed within one working day, instead of 3–4 days, and data analysis is easily conducted in high troughput conditions using up to 96 wells, while the practical operations are easy-to-handle and do not require specially trained personnel.

Conclusion

This novel MLT array is a promising alternative for high resolution and high throughput typing of C. trachomatis and will facilitate molecular epidemiology studies of chlamydia infections.
O4-S1.05 RNA helicases, p72 and p68 and HDAC1 interact with HIV-1 integrase and affect viral replication
Authors: Larguet F , Rassart É , Edouard E
Published: July 2011

Background

Human immunodeficiency virus type-1 (HIV-1) infection is one of the leading causes of death worldwide. Current anti-HIV-1 therapy, referred as highly active antiretroviral therapy (HAART), is based on the use of combination of drugs directed against viral enzymes mainly reverse transcriptase and protease and more recently integrase. Indeed, HAART has dramatically improved the clinical course of the disease. However, the emergence of multi-drug resistant virus strains during treatment highlights the urgent need to develop novel antiretroviral drugs against new HIV-1 targets. HIV-1 is able to hijack cellular machinery for its replication through protein-protein interactions between viral and host cell factors and a rising strategy against HIV-1 infection is to inhibit key virus-cell interactions. Integrase that catalyses HIV-1 viral DNA integration into the host cell genome is currently a focus for the development of new drugs. Several cellular partners of integrase have been identified using different methods. Based on a different strategy, our study aimed to identify new integrase cellular partners.

Methods

We used a biotinylated oligonucleotide derived from the viral U3 LTR end as bait to isolate integrase in a streptavidin beads magnetic separation. Proteins co-purified with integrase were analysed by mass spectrometry.

Results

Interestingly, our method allowed the identification of new cellular proteins notably p72 and p68 RNA helicases and histone deacetylase 1 (HDAC1) as integrase partners in addition to proteins already reported in literature. The interaction of p72, p68 and HDAC1 proteins with integrase was confirmed by co-immunoprecipitation. In addition, specific knockdown of p72 and p68 RNA helicases and HDAC1 were shown to affect HIV-1 replication.

Conclusions

Our data suggest that cellular proteins, p72 and p68 RNA helicases and HDAC1 facilitate HIV-1 replication through interaction with integrase.
O4-S2.01 The host response to chlamydial infection results in increased gonococcal colonisation in a novel coinfection model
Authors: Jerse A , Vonck R , Darville T
Published: July 2011

Objective

Neisseria gonorrhoeaeandChlamydia trachomatiscause similar urogenital diseases and up to 70% of individuals with gonorrhoea also have chlamydia. Using a newly developed female mouse model of coinfection, we recently reported that higher numbers ofN gonorrhoeaewere recovered from mice with a pre-existingChlamydia muridaruminfection, the mouse strain of Chlamydia, compared to mice infected withN gonorrhoeaealone. Recent studies on the host response toN gonorrhoeaeimplicate toll-like receptor 4 (TLR4) and IL17 responses as being protective againstN gonorrhoeae. Here we tested the hypothesis that the immune response to chlamydial infection makes the genital tract more permissive toN gonorrhoeae.

Methods

Using an immune-targeted RT-PCR array we screened for alterations in host gene expression during chlamydial infection of BALB/c mice that may account for the observed increase in gonococcal colonisation. Mouse genital cells were collected by vaginal swab and analysed for TLR4 expression by flow cytometry. Coinfection studies were performed in BALB/cJ (TLR4 wild type) and C.C3-TLR4LPS-d/J (TLR4 mutant) mice and the number of viable chlamydiae and gonococci recovered from each group was determined by immunofluorescence using L929 cells and quantitative culture on GC agar, respectively.

Results

Prior toN gonorrhoeaeinoculation, mice with a pre-existing chlamydial infection had decreased expression of TLR4 and antimicrobial peptide (CRAMP, SLPI) genes. Consistent with the finding of decreased TLR4expression in coinfected mice, markers of inflammation (TLR2, TNFα, IL-1ß, platelet activating factor receptor [Pafr], and IL-23α) were up-regulated only in mice infected withN gonorrhoeaealone. A significantly lower percentage of TLR4-expressing epithelial cells was detected in vaginal swabs from chlamydia-infected wild-type mice prior to gonococcal challenge, and importantly, chlamydial infection did not enhanceN gonorrhoeaeinfection of TLR4 mutant mice.

Conclusions

These data suggest the host response to chlamydial infection creates an environment that is less protective against gonococcal infection by down-regulating the expression of TLR4 and antimicrobial peptides. This work therefore further illuminates the basis of this interesting consequence of coinfection and may also help direct the development of immunomodulatory therapies against this common coinfection and its consequences on reproductive health.
O4-S2.06 A primate model ofMycoplasma genitaliumcervical infection
Authors: Totten P , Wood G , Iverson-Cabral S , Cummings P , Sweeney Y Cosgrove , Patton D
Published: July 2011

Background

Mycoplasma genitalium(MG) is a newly recognised pathogen associated with acute and persistent reproductive tract infection in men and women. Understanding of the disease mechanisms, persistence and immune avoidance of this organism is hampered by the lack of a suitable animal model.

Methods

Female pigtail macaques (Macaca nemestrina) were inoculated cervically with ∼109 genome equivalents (∼108 ccu's) of MG strain G37, then assessed at intervals over 8 weeks for the persistence of MG in lower tract specimens. Fallopian tube biopsies were collected via laparotomy at Weeks 4 and 8. Specimens were assessed for the presence of MG DNA by qPCR and for viable MG by growth in H broth and Vero cell co-cultures. Serum collected at intervals was evaluated by immunoblot and ELISA for reactivity to MG antigens. Finally the variable regions of the immunodominant surface antigens, MgpB and MgpC, were analysed by PCR cloning and sequencing to evaluate sequence variation during infection.

Results

Of the five primates inoculated cervically with MG, three were infected throughout the 8 weeks of the study, one maintained infection for 4 weeks and one resisted infection. Recovery of viable MG from lower reproductive tract sites was improved by co-culture in Vero cells followed by qPCR to measure an increase in MG genomes during culture. Growth in H broth, as determined by colour change proved an unreliable indicator of the presence of viable MG in the specimen possibly due to the presence of primate microorganisms that inhibit the growth of MG. No viable MG or MG DNA was detected in upper tract tissues in any of the primates perhaps suggesting that longer infection times or repeated inoculations are needed to achieve ascension in this model. Analysis of mgpB variable regions B and G indicated that after 8 weeks of infection the predominant expressed sequence changed from that of the G37C inoculum to 1 to 5 novel sequences consistent with recombination between the expression site and the MgPars. In contrast, no sequence variation was observed in the inoculum grown in vitro for a similar duration. Antibodies reactive with MG antigens, including the variable regions of MgpB and MgpC, were detected by immunoblot and ELISA in serum and cervical exudates.

Conclusions

The cervical inoculation model of pigtail macaques results in long-term infection and can be used to study the persistence of MG, development of antibodies and antigenic variation.
O5-S1.02 Acceptability of in SPOT and patient-delivered partner therapy among men who have sex with men seeking medical care
Authors: Kerani R , Mark F , Golden M
Published: July 2011

Background

Patient-delivered partner therapy (PDPT) and internet partner notification (PN) sites (eg, inSPOT) are being adopted in some areas to improve PN outcomes. Neither intervention has been well-studied in men who have sex with men (MSM). We evaluated the acceptability and potential efficacy of these PN strategies among MSM.

Methods

We anonymously surveyed MSM seen in an STD clinic and a private medical practice in Seattle, WA, USA. The survey presented respondents with three scenarios in which they had oral or anal sex with a new partner and were then notified and offered PDPT. A fourth scenario described PN via an inSPOT ecard.

Results

MSM completed 198 surveys. A total of 115 (58%) men reported ever being diagnosed with a bacterial STD, 100 (50%) had previously been notified by a partner of an STD exposure, and 27 (14%) reported being HIV positive. The percentage of men who indicated that they would seek medical care was higher when scenarios indicated that the respondent had symptoms of proctitis (97%–98%) than when they were asymptomatic (83%–89%) or had symptoms of pharyngitis (84%). Only 123 (62%) men said they would seek medical care if notified via an anonymous inSPOT ecard and were asymptomatic, though this rose to 98% when the question indicated that the respondent had rectal symptoms. Men were somewhat more likely to report that they would take medication given to them as PDPT if they had symptoms than if they were asymptomatic (52%–57% vs 48%–49%). The proportion of MSM who would seek medical care if asymptomatic was lower among men who said they would take PDPT (74%–84%) than among men who indicated that they would not (92%–94%, p<0.06); this pattern was not observed when questions described rectal symptoms. When asked directly if they would use inSPOT to notify partners if they had an STD, 56% said they would. However, when given multiple options and asked how they would prefer to notify partners, only 38% chose an ecard. MSM were less likely to report that they would seek a medical evaluation if notified via an anonymous ecard than via email or a signed ecard (75% vs 94%–95%).

Conclusions

These results suggest that substantial numbers of MSM are interested in using PDPT and internet partner notification sites. However, they also support concerns that PDPT may decrease recipient's likelihood of testing for HIV and syphilis, and that anonymous ecards may be less effective in prompting partners to seek medical care than other forms of PN.
O5-S1.05 Computer assisted self interviewing in a sexual health clinic as part of routine clinical care: impact on service and patient and clinician views
Authors: Vodstrcil L , Hocking J , Cummings R , Chen M , Bradshaw C , Read T , Sze J , Fairley C
Published: July 2011

Background

Computer assisted self interviewing (CASI) has been used at the Melbourne Sexual Health Centre (MSHC) in Victoria, Australia since June 2008, to obtain a pre-consultation sexual risk history. We aimed to evaluate the impact of CASI on consultation times, STI testing rates, patient response rates to CASI questions, and obtain patient and clinician views on CASI.

Methods

The proportion of patients who declined to answer questions using CASI since 2008 was calculated. We then used the same 12 week period (Feb to May) over three years (2008 pre-CASI), (2009 CASI period), and (2010 non-CASI period-due to a computer theft) to assess consultation times and STI-testing rates. We carried out surveys of clinicians and patients to determine their experience and the acceptability of CASI as part of routine clinical practice.

Results

14 190 patients completed CASI during the audit period. Men were more likely than women to decline questions about the number of partners they had of the opposite sex (4.4% v 3.6%, p=0.05) and same sex (8.9% v 0%, p<0.01). One third (34%) of HIV-positive men did not answer questions on number of partners and 18% declined questions about condom use with insertive anal sex. There was no difference in the mean consultation times during CASI and non-CASI operating periods (p?0.17). Only the proportion of women tested for chlamydia differed between CASI and non-CASI periods (p<0.01, 84% v 88% respectively). 267 patients completed the survey about CASI. Most (72% men and 69% women) were comfortable using the computer and reported that all their answers were accurate (76% men and 71% women). Half preferred CASI but 18% would have preferred a clinician to have asked the questions. 39 clinicians completed the staff survey, but a varying proportion (11%–44%) felt that face-to-face interviewing was more accurate, depending on the risk factor. Only 5% were unsatisfied with CASI.

Conclusions

This is the first evaluation of CASI operating routinely in a sexual health clinic. We have demonstrated that CASI is acceptable to most patients and clinicians in a sexual health setting and does not adversely affect various measures of clinical output. The true value of CASI is most likely to be realised when it is integrated with further innovations in clinical care such as the development of express clinical services, decision support software and detailed behavioural surveillance system.
O5-S2.01 A National Program with a National impact: quadrivalent HPV vaccination and genital warts in Australia, 2004–2010
Authors: Donovan B , Guy R , Ali H , Grulich A , Regan D , Wand H , Fairley C
Published: July 2011

Background

From mid-2007 Australia funded a universal free vaccination program for all females between 12 and 26 years, but not for men or for women who were older than 26 years in 2007. Vaccine coverage rates of >80% were achieved for school-girls, though coverage was probably lower for young women in the community. To determine the population effect of the vaccine program we established a national surveillance network to measure trends in clinical presentations for genital warts.

Methods

Eight sexual health services dispersed around Australia provided data on all new patients between 2004 and 2010, including new diagnoses of genital warts, demographics, sexual behaviour, and HPV vaccination status.

Results

Among more than 130 000 new patients we identified over 10 000 new cases of genital warts. Before the vaccination program there was no change in the proportion of women or heterosexual men diagnosed with genital warts. In the first 30 months of the vaccination program we detected a 59% decline in the proportion of young resident women diagnosed with genital warts (p-trend <0.0001) and preliminary analysis indicates that this trend was ongoing in 2010. In contrast, we could not detect any significant decline in genital warts among non-resident young women, older women, or men who have sex with men. Interestingly, the proportion of younger men (<26 years in mid-2007) diagnosed with genital warts declined by 39% (p-trend <0.0001) while there was no significant decline among older heterosexual men. By 2009, 65% of resident women of free vaccine-eligible age, 15% of non-resident women of the same age, and 11% of older women reported having had a quadrivalent or an unknown HPV vaccine.

Conclusion

The vaccination program has had a large population-level impact on the incidence of genital warts in young Australian women, with some flow-on benefit for young heterosexual men as a result of herd immunity.