Barbara Van Der Pol

Multicenter Evaluation of the BDProbeTec ET System for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in Urine Specimens, Female Endocervical Swabs, and Male Urethral Swabs

ABSTRACT The performance of the Becton Dickinson BDProbe Tec ET SystemChlamydia trachomatis and Neisseria gonorrhoeaeAmplified DNA Assays (BD Biosciences, Sparks, Md.) was evaluated in a multicenter study. Specimens were collected from 2,109 men and women, with or without symptoms, attending sexually transmitted disease, family planning, and obstetrics and gynecology clinics. Both swab and urine samples were collected, and the results obtained from 4,131 specimens were compared to those from culture and the LCx nucleic acid amplification test (Abbott Industries, Abbott Park, Ill.). PCR and cytospin of the culture transport medium with chlamydia direct fluorescent antibody staining were used to adjudicate chlamydia culture-negative results. Sensitivity and specificity were calculated both with and without use of the amplification control (AC), with little apparent difference in the results. Without the AC result, sensitivity for C. trachomatis and N. gonorrhoeae were 92.8 and 96.6%, respectively, for cervical swabs and 80.5 and 84.9% for urine from women. C. trachomatis and N. gonorrhoeae sensitivities were 92.5 and 98.5%, respectively, for male urethral swabs and 93.1 and 97.9% for urine from men. This amplified DNA system for simultaneous detection of chlamydial and gonococcal infections demonstrated superior sensitivity compared to chlamydia culture and has performance characteristics comparable to those of other commercially available nucleic acid-based assays for these organisms.

Repeated Chlamydia trachomatis Genital Infections in Adolescent Women

BACKGROUND Repeated Chlamydia trachomatis infections are common among young sexually active women. The relative frequency of reinfection and antibiotic treatment failure is undefined. METHODS Adolescent women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessments performed every 3 months, including amplification tests for C. trachomatis, ompA genotyping, and interviews and diary entries to document sex partner-specific coitus and event-specific condom use. Repeated infections were classified as reinfection or treatment failure by use of an algorithm. All infections for which treatment outcomes were known were used to estimate the effectiveness of antibiotic use. RESULTS We observed 478 episodes of infection among 210 study participants; 176 women remained uninfected. The incidence rate was 34 episodes/100 woman-years. Of the women who were infected, 121 experienced 1 repeated infections, forming 268 episode pairs; 183 pairs had complete data available and were classified using the algorithm. Of the repeated infections, 84.2% were definite, probable, or possible reinfections; 13.7% were probable or possible treatment failures; and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated 92.2% effectiveness of antibiotic use. CONCLUSIONS Most repeated chlamydial infections in this high-incidence cohort were reinfections, but repeated infections resulting from treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies.

Vaginal Swabs Are Appropriate Specimens for Diagnosis of Genital Tract Infection with Chlamydia trachomatis

ABSTRACT Because self-collected vaginal swabs (VS) are potentially very useful for screening asymptomatic women for Chlamydia trachomatis infection, a multicenter study evaluated that specimen with nucleic acid amplification tests (NAATs). The objective was to determine whether VS are equal to Food and Drug Administration (FDA)-cleared specimens (cervical swabs and first-catch urines [FCU]) for diagnosing genital chlamydial infection. All NAATs then commercially available (October 1996 to October 1999) were used (ligase chain reaction [LCx Probe System; Abbott Laboratories, Abbott Park, Ill.]; PCR [Amplicor; Roche Molecular Systems, Branchburg, N.J.]; and transcription-mediated amplification, [Amplified CT Assay; Gen-Probe Inc., San Diego, Calif.]). NAATs were performed on FCU, urethral, cervical, self- and clinician-collected VS. Sensitivity was compared to isolation using cervical and urethral swabs. Agreement of NAAT results between VS and cervical swabs or FCU was calculated. Specimens from 2,517 15- to 25-year-old asymptomatic women attending clinics at nine different centers were evaluated. Results with self- and clinician-collected VS were equivalent and were at least as good as results with FCU and cervical swabs. Across all sites, summary specificities for all specimens were >99%. Among culture-positive women, NAAT sensitivity with VS (93%) was as high as or higher than NAAT sensitivity with cervical swabs (91%) or FCU (80.6%) or culture of cervical swabs (83.5%). VS are appropriate specimens for diagnosing chlamydial genital tract infection by NAATs. That patients can efficiently collect them offers important benefits for screening programs. It would be beneficial for public health programs if the NAAT manufacturers sought FDA clearance for this specimen.

Prevalence, Incidence, Natural History, and Response to Treatment of Trichomonas vaginalis Infection among Adolescent Women

BACKGROUND Trichomonas vaginalis infection is a sexually transmitted infection (STI) linked with reproductive health complications. However, few data exist concerning the epidemiologic profile of this pathogen in adolescent women, a group at high risk for other STIs. METHODS Our objective was to describe the prevalence, incidence, natural history, and response to treatment of T. vaginalis infection in adolescent women. Women 14-17 years old were followed for up to 27 months. Vaginal swab samples were obtained during quarterly clinic visits and were self-obtained weekly during 12-week diary collection periods. The weekly samples were tested quarterly. Infections were identified by polymerase chain reaction and were treated with 2.0 g of oral metronidazole. Analysis was performed on the subset of participants who returned for at least 1 quarterly clinic visit. RESULTS T. vaginalis infection was identified in 6.0% (16/268) of the participants at enrollment. Overall, 23.2% (57/245) of the participants with at least 3 months of follow-up had at least 1 infection episode; 31.6% (18/57) experienced multiple episodes. Seventy-two incident infection episodes were diagnosed. When treatment was not documented, weekly samples from participants were positive for up to 12 consecutive weeks. After treatment, T. vaginalis DNA was undetectable within 2 weeks in all but 3 participants. CONCLUSIONS The incidence of T. vaginalis infection is high among adolescent women; untreated infections may last undetected for 3 months or longer. Reinfection is common. Treatment with oral metronidazole is effective, and T. vaginalis DNA disappears rapidly after treatment.

Performance of the Cepheid CT/NG Xpert Rapid PCR Test for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae

ABSTRACT Tests for Chlamydia trachomatis and Neisseria gonorrhoeae, which can provide results rapidly to guide therapeutic decision-making, offer patient care advantages over laboratory-based tests that require several days to provide results. We compared results from the Cepheid GeneXpert CT/NG (Xpert) assay to results from two currently approved nucleic acid amplification assays in 1,722 female and 1,387 male volunteers. Results for chlamydia in females demonstrated sensitivities for endocervical, vaginal, and urine samples of 97.4%, 98.7%, and 97.6%, respectively, and for urine samples from males, a sensitivity of 97.5%, with all specificity estimates being ≥99.4%. Results for gonorrhea in females demonstrated sensitivities for endocervical, vaginal, and urine samples of 100.0%, 100.0%, and 95.6%, respectively, and for urine samples from males, a sensitivity of 98.0%, with all estimates of specificity being ≥99.8%. These results indicate that this short-turnaround-time test can be used to accurately test patients and to possibly do so at the site of care, thus potentially improving chlamydia and gonorrhea control efforts.

Trichomonas vaginalis Infection: The Most Prevalent Nonviral Sexually Transmitted Infection Receives the Least Public Health Attention

Trichomonas vaginalis infection was first described as a venereal disease in themid-20th century decades before Chlamydia trachomatis infection would be recognized as such. The motile protozoan responsible for trichomoniasis in women is easily viewed with unsophisticated microscopy. Unfortunately this leads to the impression that because these organisms are large motile and easily seen wet preparation microscopy is highly sensitive. This ignores the high organism load necessary for vaginal sampling to capture organisms. Because wet preparations with positive results are obtained from women with high organism loads it is not surprising that the majority of these women are symptomatic. As a result of this asymptomatic women are rarely tested outside of sexually transmitted infection (STI) clinic settings. Since the development of nucleic acid amplification tests for T. vaginalis DNA our understanding of the epidemiology of this pathogen has improved and suggests that as many as one-third of infections in women may be asymptomatic. (excerpt)

Characteristic Male Urine Microbiomes Associate with Asymptomatic Sexually Transmitted Infection

Background The microbiome of the male urogenital tract is poorly described but it has been suggested that bacterial colonization of the male urethra might impact risk of sexually transmitted infection (STI). Previous cultivation-dependent studies showed that a variety of non-pathogenic bacteria colonize the urethra but did not thoroughly characterize these microbiomes or establish links between the compositions of urethral microbiomes and STI. Methodology/Findings Here, we used 16S rRNA PCR and sequencing to identify bacteria in urine specimens collected from men who lacked symptoms of urethral inflammation but who differed in status for STI. All of the urine samples contained multiple bacterial genera and many contained taxa that colonize the human vagina. Uncultivated bacteria associated with female genital tract pathology were abundant in specimens from men who had STI. Conclusions Urine microbiomes from men with STI were dominated by fastidious, anaerobic and uncultivated bacteria. The same taxa were rare in STI negative individuals. Our findings suggest that the composition of male urine microbiomes is related to STI.

Bacterial vaginosis and vaginal yeast, but not vaginal cleansing, increase HIV-1 acquisition in African women

Objective:To evaluate interrelationships between bacterial vaginosis (BV), vaginal yeast, vaginal practices (cleansing and drying/tightening), mucosal inflammation, and HIV acquisition. Methods:A multicenter, prospective, observational cohort study was conducted, enrolling 4531 HIV-negative women aged 18 to 35 years attending family planning clinics in Zimbabwe and Uganda. Participants were tested for HIV and reproductive tract infections and were interviewed about vaginal practices every 3 months for 15 to 24 months. BV was measured by Gram stain Nugent scoring, vaginal yeast by wet mount, and mucosal inflammation by white blood cells on Gram stain. Results:HIV incidence was 4.12 and 1.53 per 100 woman-years of follow-up in Zimbabwe and Uganda, respectively (a total of 213 incident infections). Women with BV or vaginal yeast were more likely to acquire HIV, especially if the condition was present at the same visit as the new HIV infection and the visit preceding it (hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.68 to 3.72 and HR = 2.97, 95% CI: 1.67 to 5.28 for BV and yeast, respectively). These relationships did not seem to be mediated by mucosal inflammation. Vaginal drying/tightening was associated with HIV acquisition in univariate (HR = 1.49, 95% CI: 1.03 to 2.15) but not multivariate models. Vaginal cleansing was not associated with HIV acquisition. Conclusions:BV and yeast may contribute more to the HIV epidemic than previously thought.

From the NIH: proceedings of a workshop on the importance of self-obtained vaginal specimens for detection of sexually transmitted infections.

On June 27, 2006, the NIH conducted a workshop to review published data and current field practices supporting the use of self-obtained vaginal swabs (SOVs) as specimens for diagnosis of sexually transmitted infections (STIs). The workshop also explored the design of studies that could support FDA clearance of SOVs for STI testing, particularly for specimens collected in nonclinical settings including patients’ homes. This report summarizes the workshop findings and recommendations. Participants concluded that self-obtained vaginal swabs are well accepted by women of all ages and that SOVs perform as well as or better than other specimen types for Chlamydia trachomatis and Neisseria gonorrhoeae detection using transcription-mediated amplification. In addition, workshop participants recommended the validation of SOV testing by public health practitioners and manufacturers of STI diagnostic tests to expedite incorporation of SOVs as a diagnostic option in clinical and nonclinical settings for Chlamydia trachomatis and Neisseria gonorrhoeae testing. Similarly, SOVs should be explored for use in the diagnosis of other sexually transmitted pathogens.

Disentangling contributions of reproductive tract infections to HIV acquisition in African women.

Objective: To estimate the effects of reproductive tract infections (RTIs) on HIV acquisition among Zimbabwean and Ugandan women. Methods: A multicenter prospective observational cohort study enrolled 4439 HIV-uninfected women aged 18 to 35 attending family planning clinics in Zimbabwe and Uganda. Participants were interviewed, and tested for HIV and RTIs every 3 months for 15 to 24 months. They received HIV risk reduction counseling, male condoms, and treatment for curable RTIs. Results: Despite HIV risk reduction counseling and regular screening and treatment for RTIs, the HIV incidence did not decline during the study. Positive HSV-2 serostatus at baseline (hazard ratio [HR] = 3.69, 95% confidence interval = 2.45–5.55), incident HSV-2 (HR = 5.35, 3.06–9.36), incident Neisseria gonorrhoeae (HR = 5.46, 3.41–8.75), and altered vaginal flora during the study (bacterial vaginosis [BV]: HR = 2.12, 1.50–3.01; and intermediate flora: HR = 2.02, 1.39–2.95) were independently associated with HIV acquisition after controlling for demographic and behavioral covariates and other RTIs (Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, and vaginal yeasts). For N. gonorrhoeae, C. trachomatis, T. vaginalis, and vaginal yeasts, the risk of HIV acquisition increased when the infection was identified at the visit before the HIV-detection visit or with the duration of infection. Population attributable risk percent (PAR%) calculations show that HSV-2 contributes most to acquisition of new HIV infections (50.4% for baseline HSV-2 and 7.9% for incident HSV-2), followed by altered vaginal flora (17.2% for bacterial vaginosis and 11.8% for intermediate flora). Conclusions: A substantial proportion of new HIV infections in Zimbabwean and Ugandan women are attributable to RTIs, particularly HSV-2 and altered vaginal flora.