Marcia M. Hobbs

The transferrin receptor expressed by gonococcal strain FA1090 is required for the experimental infection of human male volunteers

Iron, an essential nutrient for most microorganisms, is sequestered by the host to decrease the concentration of iron available to bacterial pathogens. Neisseria gonorrhoeae, the causative agent of gonorrhoea, can acquire iron by direct interaction with human iron‐binding proteins, including the serum glycoprotein, transferrin. Iron internalization from host transferrin requires the expression of a bacterial receptor, which specifically recognizes the human form of transferrin. Two gonococcal transferrin‐binding proteins have been implicated in transferrin receptor function, TbpA and TbpB. We constructed a gonococcal transferrin receptor mutant without the introduction of additional antibiotic resistance markers and tested its ability to cause experimental urethritis in human male volunteers. The transferrin receptor mutant was incapable of initiating urethritis, although the same inoculum size of the wild‐type parent strain, FA1090, causes urethritis in >90% of inoculated volunteers. To our knowledge, this is the first experimental demonstration that a bacterial iron acquisition system is an essential virulence factor for human infection.

Rapid Antigen Testing Compares Favorably with Transcription-Mediated Amplification Assay for the Detection of Trichomonas vaginalis in Young Women

BACKGROUND Diagnosis of Trichomonas vaginalis (TV) infection is limited by imperfect testing methods. Newer tests, such as rapid antigen and nucleic acid amplification tests, are often compared with culture, which is not widely used but is more sensitive than wet mount. We assessed the sensitivity and specificity of 4 tests for the identification of TV using 3 statistical approaches. METHODS Sexually active adolescent women aged 14-21 years (n=330) were recruited from a teen health center and emergency department. Vaginal swabs were tested for TV using wet mount, culture (InPouch TV; Biomed Diagnostics), rapid antigen testing (OSOM TV; Genzyme Diagnostics), and transcription-mediated amplification testing (TMA; APTIMA TV analyte specific reagents; Gen-Probe). RESULTS TV was detected in 61 participants (18.5%). Compared with a composite reference standard (i.e., any TV test with positive results), the sensitivities of wet mount, culture, rapid antigen testing, and TMA were 50.8%, 75.4%, 82%, and 98.4%, respectively. Using latent class analysis, the sensitivity of wet mount (56%) was significantly lower than that of other tests, and the sensitivities of culture and rapid antigen testing were similar (83% and 90%, respectively); specificity was 100% for each of these 3 methods. TMA had a sensitivity of 98.2% and a specificity of 98%. Tests performed equally well regardless of whether the participant had bleeding or other infections. The sensitivities of the rapid antigen test and TMA were comparable (92.5% and 97.5%, respectively) in women who had vaginal symptoms. CONCLUSIONS Wet mount alone is insufficient for the reliable diagnosis of TV infection in women. TMA and rapid antigen tests are highly sensitive and specific, and both are superior to wet mount. Rapid antigen testing is equivalent to culture, and it compares favorably with the sensitivity of TMA for the detection of TV.

A Randomized, Double-Blind, Placebo-Controlled Trial of Combined Nevirapine and Zidovudine Compared with Nevirapine Alone in the Prevention of Perinatal Transmission of HIV in Zimbabwe

Background. Trichomonas vaginalis causes a common sexually transmitted infection (STI) in women, yet trichomoniasis in male sexual partners is not well recognized. Nucleic acid amplification tests can increase detection of T. vaginalis in men compared with culture.Methods. We conducted a prospective, multicenter study to evaluate T. vaginalis infection among male partners of women with trichomoniasis and factors associated with infection by recruiting patients from 3 public clinics in the United States. Male partners were tested for concordant T. vaginalis infection, defined as a positive urethral culture, urine culture, or urine polymerase chain reaction (PCR) result. A subset of men also provided a semen sample for T. vaginalis culture and PCR. Factors associated with concordant infection were determined from bivariable and multivariable analyses.Results. We enrolled 540 women with trichomoniasis (diagnosed using wet mount microscopy and/or culture) and 261 (48.4%) of their male partners. T. vaginalis infection was detected in 177 (71.7%) of 256 male partners (95% confidence interval [CI], 66.0%– 77.3%), of whom 136 (77.3%) were asymptomatic. A vaginal pH of >4.5 in a woman was independently associated with infection in the male partner (adjusted odds ratio, 2.5; 95% CI, 1.0– 6.3). Younger male age (20– 29 and 30– 39 years) was also found to be an independent risk factor for concordant trichomoniasis.Conclusions. The majority of male partners of women with trichomoniasis were infected; however, few factors predicted infection. T. vaginalis causes a highly prevalent STI, necessitating vastly improved partner management, application of sensitive nucleic-acid based testing, and better clinical recognition.

Trichomonas vaginalis as a cause of urethritis in Malawian men.

BACKGROUND AND OBJECTIVES Trichomonas vaginalis is one of the most common sexually transmitted infections. In Malawi, rates of trichomoniasis in women are high. The prevalence of T. vaginalis infection in men is expected to be high but has not previously been documented. GOALS We sought to determine the prevalence of trichomoniasis in Malawian men with and without urethritis, to evaluate a polymerase chain reaction detection assay for T. vaginalis in urethral swabs and to examine the effect of T. vaginalis infection on excretion of human immunodeficiency virus (HIV) in semen. STUDY DESIGN Men presenting at the Sexually Transmitted Diseases (STD) and Dermatology Clinics in Malawi were enrolled in a cross-sectional study. We compared a polymerase chain reaction-based test for T. vaginalis detection with wet-mount microscopy and culture of urethral swabs. HIV serology was determined by enzyme-linked immunosorbent assay (ELISA), and HIV-1 RNA concentrations in semen were measured by quantitative nucleic acid sequence-based analysis. RESULTS T. vaginalis was detected in 51 of 293 men. The estimated prevalence among symptomatic men was 20.8% and among asymptomatic men, 12.2%. Polymerase chain reaction performed with a sensitivity of 0.82 (95% CI: 0.66-0.92) and specificity of 0.95 (95% CI: 0.91-0.97) compared to wet-mount microscopy and culture. There was no difference in the rate of HIV seropositivity in men with and without T. vaginalis infection. However, in men with symptomatic urethritis, the median HIV RNA concentration in seminal plasma from men with T. vaginalis was significantly higher that in seminal plasma from HIV-positive men without trichomonas.

Biomarker Validation of Reports of Recent Sexual Activity: Results of a Randomized Controlled Study in Zimbabwe

Challenges in the accurate measurement of sexual behavior in human immunodeficiency virus (HIV) prevention research are well documented and have prompted discussion about whether valid assessments are possible. Audio computer-assisted self-interviewing (ACASI) may increase the validity of self-reported behavioral data. In 2006-2007, Zimbabwean women participated in a randomized, cross-sectional study that compared self-reports of recent vaginal sex and condom use collected through ACASI or face-to-face interviewing (FTFI) with a validated objective biomarker of recent semen exposure (prostate-specific antigen (PSA) levels). Of 910 study participants, 196 (21.5%) tested positive for PSA, an indication of semen exposure during the previous 2 days. Of these 196 participants, 23 (11.7%) reported no sex in the previous 2 days, with no difference in reported sexual activity between interview modes (12.5% ACASI vs. 10.9% FTFI; Fishers exact test: P = 0.72). In addition, 71 PSA-positive participants (36.2%) reported condom-protected vaginal sex only; their reports also indicated no difference between interview modes (33.7% ACASI vs. 39.1% FTFI; P = 0.26). Only 52% of PSA-positive participants reported unprotected sex during the previous 2 days. Self-report was a poor predictor of recent sexual activity and condom use in this study, regardless of interview mode, providing evidence that such data should be interpreted cautiously.

Trichomoniasis: clinical manifestations, diagnosis and management

Trichomonas vaginalis was originally considered a commensal organism until the 1950s when the understanding of its role as a sexually transmitted infection (STI) began to evolve. Trichomoniasis has been associated with vaginitis, cervicitis, urethritis, pelvic inflammatory disease (PID), and adverse birth outcomes. Infection with T vaginalis could have an important role in transmission and acquisition of HIV. T vaginalis is site specific for the genitourinary tract and has been isolated from virtually all genitourinary structures. Asymptomatic disease is common in both men and women, thus screening for disease is important. Various sociodemographic factors have been correlated with presence of T vaginalis, and may be used to predict infection. Diagnosis is usually made from wet mount microscopy and direct visualisation, which are insensitive. DNA amplification techniques perform with good sensitivity, but are not yet approved for diagnostic purposes. In areas where diagnostic methods are limited, management of trichomoniasis is usually as part of a clinical syndrome; vaginal discharge for women and urethral discharge for men. A single dose of metronidazole is effective in the majority of cases. Outside of the United States, other nitroimidazoles may be used and are as effective as metronidazole. Metronidazole resistance is an emerging problem, but its clinical importance is not yet clear. Concomitant treatment of sexual partners is recommended.

The prevalence of trichomoniasis in young adults in the United States

Background and Objectives: The prevalence of trichomoniasis in the general population of the United States is unknown. This study provides the first population-based prevalence estimates of trichomoniasis among young adults in the United States. Methods: The National Longitudinal Study of Adolescent Health (Add Health) is an ongoing prospective cohort study. In a cross-sectional analysis of Wave III of Add Health (N = 12,449), we determined the prevalence of trichomoniasis using a polymerase chain reaction assay. Results: The estimated overall prevalence of trichomoniasis in U.S. young adults was 2.3% (95% confidence interval [CI], 1.8–2.7%). The prevalence was slightly higher among women (2.8%; 95% CI, 2.2–3.6%) than men (1.7%; 95% CI, 1.3–2.2%). The prevalence increased with age and varied by region, with the south having the highest prevalence (2.8%; 95% CI, 2.2–3.5%). The prevalence was highest among black women (10.5%; 95% CI, 8.3–13.3%) and lowest among white women (1.1%; 95% CI, 0.8–1.6%). Among men, the prevalence was highest among Native Americans (4.1%; 95% CI, 0.4–29.3%) and blacks (3.3%; 95% CI, 2.2–4.9%), and lowest among white men (1.3%; 95% CI, 0.9–1.8%). Conclusions: Trichomoniasis is moderately prevalent among the general U.S. population of young adults and disturbingly high among certain racial/ethnic groups.

Use of an Immunochromatographic Assay for Rapid Detection of Trichomonas vaginalis in Vaginal Specimens

ABSTRACT Trichomonas vaginalis infection is estimated to be the most widely prevalent nonviral sexually transmitted infection in the world. Wet-mount microscopy is the most common diagnostic method, although it is less sensitive than culture. The OSOM Trichomonas Rapid Test (Genzyme Diagnostics, Cambridge, Mass.) (referred to here as OSOM) is a new point-of-care diagnostic assay for T. vaginalis that uses an immunochromatographic capillary flow (dipstick) assay and provides results in 10 min. The purpose of this study was to determine the test characteristics of OSOM compared to those of a composite reference standard (CRS) comprised of wet-mount microscopy and T. vaginalis culture. This multicenter cross-sectional study enrolled sexually active women ≥18 years of age who presented with symptoms of vaginitis, exposure to T. vaginalis, or multiple sexual partners. Vaginal-swab specimens were obtained for T. vaginalis culture, wet mount, and rapid testing. The prevalence of T. vaginalis in this sample was 23.4% (105 of 449) by the CRS. The sensitivity and specificity of OSOM vaginal-swab specimens were 83.3 and 98.8%, respectively, while wet mount had a sensitivity and specificity of 71.4 and 100%, respectively, compared to the CRS. OSOM performed significantly better than wet mount (P = 0.004) and detected T. vaginalis in samples that required 48 to 72 h of incubation prior to becoming culture positive. The performance of the rapid test was not affected by the presence of coinfections with chlamydia and gonorrhea. The OSOM Trichomonas Rapid Test is a simple, objective test that can be expected to improve the diagnosis of T. vaginalis, especially where microscopy and culture are unavailable.

Molecular Testing for Trichomonas vaginalis in Women: Results from a Prospective U.S. Clinical Trial

ABSTRACT Trichomoniasis is a common sexually transmitted disease associated with preterm birth, low birth weight, and increased susceptibility to infection with other pathogenic sexually transmitted microorganisms. Nucleic acid amplification tests for Trichomonas vaginalis have improved sensitivity for detecting infected individuals compared to existing culture-based methods. This prospective, multicenter U.S. clinical trial evaluated the performance of the automated Aptima T. vaginalis assay for detecting T. vaginalis in 1,025 asymptomatic and symptomatic women. Vaginal swab, endocervical swab, ThinPrep PreservCyt, and urine specimens were collected. Subject infection status was determined by wet-mount microscopy and culture. Aptima T. vaginalis assay performance was determined for each specimen type by comparison to subject infection status. Of 933 subjects analyzed, 59.9% were symptomatic. Aptima T. vaginalis clinical sensitivity and specificity were, respectively, 100% and 99.0% for vaginal swabs, 100% and 99.4% for endocervical swabs, 100% and 99.6% in ThinPrep samples, and 95.2% and 98.9% in urine specimens. Aptima T. vaginalis performance levels were similar in asymptomatic and symptomatic subjects. This study validates the clinical performance of the Aptima T. vaginalis assay for screening asymptomatic and symptomatic women for T. vaginalis infection.

Prostate-specific antigen to ascertain reliability of self-reported coital exposure to semen

Objective: The objective of this study was to assess the validity of women’s reports of recent unprotected sex by testing for prostate-specific antigen (PSA) in vaginal samples. Study Design: The authors conducted prospective research with 332 female sex workers attending 2 public dispensaries in Madagascar. Results: Among women who reported no sex or protected sex only within the past 48 hours, 21% and 39%, respectively, tested positive for PSA. Among those testing positive for PSA, no differences in PSA concentrations were found among those reporting no sex, protected sex only, or at least one unprotected act. Conclusions: The substantial disagreement between self-reports and measurement of a biologic marker of semen exposure in vaginal specimens substantiates that self-reports of sexual behavior cannot be assumed to be valid measures. Future sexually transmitted infection/HIV and pregnancy prevention studies should confirm the validity of self-reports or use end points that do not rely on self-reported data.