Longitudinal assessment of nonavalent vaccine HPV types in a sample of sexually active African American women from ten U.S. Cities.

BACKGROUND: Chronic infection with high-risk human papillomavirus is a necessary cause for cervical carcinogenesis. This study examined prevalence of nonavalent vaccine preventable HPV types over four months among sexually active women in the United States. METHODS: This sub-study obtained meta-data for 80 of the 1,365 women (18-25 years), enrolled in the BRAVO study, a randomized, open-label trial of home screening and treatment of asymptomatic bacterial vaginosis at high-risk for sexually transmitted infections conducted between 2008 and 2013. Participants were randomized to treatment or standard-of-care, and followed every 2-months for 12 months. Stored vaginal swabs from the first three visits were tested for the nine vaccine preventable HPV types using quantitative PCR. Prevalence and associated 95% confidence intervals for the HPV types were assessed using R (version 3.6.1). RESULTS: The average age of the participants was 21.5 (SD ± 2.11) years, with 60% having ever been pregnant and all were African-American. Majority (71%) reported ≥ two sex partners in the prior year with 89% having unprotected vaginal sex and 45% having a new sex partner in the prior year. About 30% had ≥ one of the nine nonavalent vaccine HPV types at all three time points over a period of four months, 15% at two of any three visits, 19% at one of the three visits and 36% were negative for all nine vaccine HPV types at all time points. The most frequently detected HPV vaccine types were 52, 58, 16, and 18. The prevalence of any vaccine HPV types, and high-risk HPV types was 63.8% and 58.8%, respectively. CONCLUSIONS: Our findings suggest that HPV vaccination which is currently recommended for all unvaccinated persons through age 26 years, is likely to be more beneficial than previously thought as nonavalent HPV vaccine was not available during the time these data were collected.

Clinical performance of the Solana® Point-of-Care Trichomonas Assay from clinician-collected vaginal swabs and urine specimens from symptomatic and asymptomatic women.

BACKGROUND: Solana® (Quidel) is a new rapid (<40 min.) point-of-care (POC) test for qualitative detection of Trichomonas vaginalis (TV) DNA. The assay has two steps: 1) specimen preparation, and 2) amplification and detection using isothermal Helicase-Dependent Amplification (HDA). The objective was to demonstrate the performance of Solana for vaginal swabs and female urines based on comparison to wet mount and TV culture. Performance was also compared to the Aptima-TV assay. METHODS: Urine and four clinician-collected vaginal swabs were collected. The first two were used for FDA composite reference (wet mount; InPouch TV Culture). The third swab was used for Solana. Sensitivity/specificity were based on the reference method. A specimen was considered positive if either test was positive. The fourth swab was for Aptima-TV. RESULTS: Vaginal swabs and urines were obtained from 501 asymptomatic and 543 symptomatic women. Prevalence of TV by was 11.5%. For swabs, Solana® demonstrated high sensitivity and specificity from asymptomatic (100%/98.9%) and symptomatic (98.6%/98.5%) women, as well as for urines from asymptomatic (98.0%/98.4%) and symptomatic (92.9%/97.9%) women, compared to the reference method. Compared to Aptima-TV, the sensitivity/specificity was 89.7%/99.0% for swabs and 100%/98.9% for urines. CONCLUSION: The Solana® assay performed well compared to the reference assays.

Vaginal leucocyte counts in women with bacterial vaginosis: relation to vaginal and cervical infections.

OBJECTIVES: To evaluate whether an elevated vaginal leucocyte count in women with bacterial vaginosis (BV) predicts the presence of vaginal or cervical infections, and to assess the relation of vaginal WBC counts to clinical manifestations. METHODS: We retrospectively analysed the relation of vaginal leucocyte counts to vaginal and cervical infections and to clinical manifestations in non-pregnant women diagnosed with BV at an STD clinic visit. RESULTS: Of 296 women with BV studied, the median age was 24 years and 81% were African-American. Elevated vaginal leucocyte counts were associated with objective signs of vaginitis and cervicitis and also predicted candidiasis (OR 7.9, 95% CI 2.2 to 28.9), chlamydia (OR 3.1, 95% CI 1.4 to 6.7), gonorrhoea (OR 2.7, 95% CI 1.3 to 5.4), or trichomoniasis (OR 3.4, 95% CI 1.6 to 7.3). In general, as a screening test for vaginal or cervical infections, vaginal leucocyte count had moderate sensitivities and specificities, low positive predictive values, and high negative predictive values. CONCLUSIONS: An elevated vaginal leucocyte count in women with BV was a strong predictor of vaginal or cervical infections. Vaginal leucocyte quantification may provide an alternative approach to assessing need for empirical therapy for chlamydia and gonorrhoea, particularly in resource-limited high STD risk settings that provide syndromic management.

An international study of the interobserver variation between interpretations of vaginal smear criteria of bacterial vaginosis.

An international workshop on vaginal smear-based diagnosis of bacterial vaginosis was organized where 13 investigators scoring 258 slides with smears from vaginal fluid. Interobserver reproducibility of interpretations of Nugent scores, Hay/Ison scores and wet smear scores for the diagnosis of bacterial vaginosis was shown to be high. Detailed analysis of individual scoring results however indicated that basic standards of quality control to ensure robust individual readings of slides must be adhered to.

Detection of trichomonosis in vaginal and urine specimens from women by culture and PCR.

Vaginal trichomonosis is a highly prevalent infection which has been associated with human immunodeficiency virus acquisition and preterm birth. Culture is the current "gold standard" for diagnosis. As urine-based testing using DNA amplification techniques becomes more widely used for other sexually transmitted diseases (STDs) such as gonorrhea and chlamydia, a similar technique for trichomonosis would be highly desirable. Women attending an STD clinic for a new complaint were screened for Trichomonas vaginalis by wet-preparation (wet-prep) microscopy and culture and for the presence of T. vaginalis DNA by specific PCR of vaginal and urine specimens. The presence of trichomonosis was defined as the detection of T. vaginalis by direct microscopy and/or culture from either vaginal samples or urine. The overall prevalence of trichomonosis in the population was 28% (53 of 190). The sensitivity and specificity of PCR using vaginal samples were 89 and 97%, respectively. Seventy-four percent (38 of 51) of women who had a vaginal wet prep or vaginal culture positive for trichomonads had microscopic and/or culture evidence of the organisms in the urine. Two women were positive for trichomonads by wet prep or culture only in the urine. The sensitivity and specificity of PCR using urine specimens were 64 and 100%, respectively. These results indicate that the exclusive use of urine-based detection of T. vaginalis is not appropriate in women. PCR-based detection of T. vaginalis using vaginal specimens may provide an alternative to culture.

InTray GC medium versus modified Thayer-Martin agar plates for diagnosis of gonorrhea from endocervical specimens.

A new self-contained medium system for the cultivation of Neisseria gonorrhoeae was compared to modified Thayer-Martin medium for the diagnosis of gonorrhea from endocervical specimens. There was no difference in the ability of the two methods to support the growth of N. gonorrhoeae.

Patterns of Chlamydia trachomatis testing and follow-up at a University Hospital Medical Center.

OBJECTIVE: Although testing for Chlamydia trachomatis is encouraged and increasingly practiced at sexually transmitted disease (STD) and family planning clinics, patterns of testing and follow-up in other settings are not well described. To begin to address these issues, we performed a chart review of patients with a positive laboratory test for C. trachomatis at a major university medical center. METHODS: Chart review of medical records for all patients with positive laboratory tests for C. trachomatis during calendar year 1996. RESULTS: Of 326 patients with positive tests, 95% were female and 5% were male. Median age was 22 for females and 25 for males. Most positive C. trachomatis test results were from the emergency room (ER)/walk-in clinic (55%) or patients receiving obstetric/gynecologic (OB/GYN) care (31%). While most C. trachomatis tests performed were on patients who had symptoms, patterns of treatment varied between sites. Fifty-seven percent of ER/walk-in patients received empiric antibiotics at the initial visit versus 36% of patients under OB/GYN care. Among patients with positive screening tests seen in the ER/walk-in clinic, 32% of patients had no treatment documented versus 14% of OB/GYN patients. Four percent of women with positive tests who did not receive therapy at the time of their initial evaluation developed pelvic inflammatory disease in the interval between testing and return to the medical center. CONCLUSIONS: Of the patients with positive chlamydial screening tests, the proportion not treated was similar to that found in studies performed in STD clinics.

PIP: A chart review of patients with positive laboratory tests for C. trachomatis at the University of Alabama at Birmingham Hospital and affiliated clinics during 1996 was performed to determine whether the problem of failure to notify patients of positive sexually transmitted disease (STD) test results is generalizable beyond STD clinics. Furthermore, it would review chlamydia testing practices in nonreproductive health setting. Findings revealed that of the 326 patients with positive tests, 95% were females aged 22 years and 5% were males aged 25 years. Most positive C. trachomatis test results were 51% from the emergency room (ER) and 31% from obstetric/gynecologic (OB/GYN). 57% of ER patients and 36% of OB/GYN patients received antibiotics on their initial visits. Among patients with positive screening tests, 32% of ER patients and 14% of OB/GYN patient had no documented treatment. 4% of women with positive tests, who did not receive therapy at the time of their initial evaluation, developed pelvic inflammatory disease in the interval between testing and returning to the medical center. From the findings, a substantial proportion of patients with positive screening tests for C. trachomatis may not receive timely treatment of their infections, which suggests that the problem occurs in settings other than STD and family clinics.

Comparison of direct inoculation and Copan transport systems for isolation of Neisseria gonorrhoeae from endocervical specimens.

Two commercial swab transport systems, Copan Amies gel agar with and without charcoal (Copan Diagnostics, Corona, Calif.), were compared to direct inoculation onto modified Thayer-Martin medium for detection of Neisseria gonorrhoeae in 1,490 endocervical specimens obtained from women attending a sexually transmitted disease clinic. Copan swabs were held in the transport system for 24 h at room temperature prior to inoculation onto modified Thayer-Martin medium. All cultures were incubated at 35 degrees C in 5% CO(2), and bacteria were identified on the basis of Gram stain, oxidase, and biochemical reactions. Copan Amies gel agar transport system without charcoal detected 77 of 81 (95%) direct inoculation culture-positive specimens, and Copan Amies gel agar transport system with charcoal detected 53 of 56 (95%) directly inoculated culture-positive specimens. Copan Amies gel agar without charcoal inoculated after 6 h supported growth of 56 (98%) positive cultures out of only 55 directly inoculated culture-positive specimens. This study demonstrates that Copan swabs represent a reasonable alternative, providing convenience, low cost, and ease of use while still maintaining a satisfactory recovery rate of N. gonorrhoeae from clinical specimens, if specimens can be inoculated onto selective media within a relatively short time period not involving overnight shipment.

Correlation of behaviors with microbiological changes in vaginal flora.

Bacterial vaginosis (BV) is characterized by dramatic changes in the vaginal ecosystem. Women without evidence of vaginal infection may exhibit transient changes in their flora. We prospectively followed up women by using diaries and self-obtained vaginal smears to correlate behaviors with changes in flora. The majority of women (38/51, 78%) had significant, although transient, changes. Behaviors associated with unstable flora were a history of BV, a greater number of partners, and more frequent episodes of receptive oral sex. Only the latter remained significantly associated in the multivariate analysis. Variables that were associated with day-to-day variability in the flora included use of vaginal medication, menses, greater number of partners, spermicide use, more frequent vaginal intercourse, and less frequent use of condoms. Only a minority of women (11/51, 22%) maintained a "normal" lactobacillus-predominant flora. Factors associated with instability of the flora are similar to those epidemiologically associated with BV.

Validity of self-obtained vaginal specimens for diagnosis of trichomoniasis.

A comparison of self- and clinician-collected vaginal specimens for the diagnosis of trichomoniasis was conducted. The sensitivities of culture methods using self- and clinician-collected specimens were 84.6 and 88.5%, respectively. There was no significant difference between the sensitivities of culture methods using self- and clinician-collected vaginal specimens for the diagnosis of trichomoniasis.

Positive screening tests for gonorrhea and chlamydial infection fail to lead consistently to treatment of patients attending a sexually transmitted disease clinic.

BACKGROUND AND OBJECTIVES: Patients attending sexually transmitted disease (STD) clinics are frequently screened for gonorrhea and chlamydial infection. To determine the efficiency of these screening efforts as a component of STD control, we evaluated treatment outcomes of patients with positive cultures who had not received presumptive treatment at their initial visit. GOALS: To determine the treatment outcomes of patients screened for STDs who have positive test results. STUDY DESIGN: Retrospective chart review of the computerized medical record. RESULTS: Between January 1, 1994 and June 30, 1995, 24,823 patients were tested for gonorrhea, of whom 19.3% (4791) had positive cultures. Of patients with positive gonorrhea cultures, 564 (11.8%) had positive screening cultures and did not receive therapy at the time of evaluation. Similarly, screening chlamydial cultures were positive in 1539 (10.9%) of 14,162 patients screened for chlamydial infection. Forty-four percent (677) of these did not receive presumptive treatment for chlamydial infection at their initial visit. Overall, 20% of patients with positive cultures failed to return to the clinic for treatment within 30 days of screening. Of those who did return, 30% did so only after at least 2 weeks had elapsed. CONCLUSIONS: A substantial proportion of patients with positive screening tests for gonorrhea and chlamydial infection fail to comply with follow-up recommendations and thus are likely to remain infectious. Methods must be sought to enhance patient compliance with follow-up of test results and treatment if indicated.

The use of sequential self-obtained vaginal smears for detecting changes in the vaginal flora.

BACKGROUND AND OBJECTIVES: The ability to study daily changes in the vaginal flora may provide insight into the pathogenesis of bacterial vaginosis. Because culture of the vaginal fluid is tedious and expensive, the utility of self-obtained vaginal smears for documenting changes in the flora was evaluated. GOALS: To validate the adequacy of self-collected vaginal fluid Gram stains and use them to monitor vaginal flora. STUDY DESIGN: Ten asymptomatic premenopausal women collected daily vaginal smears for 30 days. The smears were Gram stained and interpreted using a standardized scoring system (Nugent criteria). In addition, results from self- and clinician-obtained vaginal smears from 18 women were compared to validate the adequacy of self-obtained smears. RESULTS: Two women had asymptomatic bacterial vaginosis. One woman, who was postpartum, had intermediate flora that toward the end of the collection period changed to Lactobacillus predominant. The remaining seven women exhibited two patterns. One was Lactobacillus morphotypes only; the second consisted of Lactobacillus-predominant days interspersed with days with moderate to high numbers of Gardnerella/Bacteroides morphotypes. There was a significant correlation of the point of change in the flora of this group with menses. CONCLUSIONS: The adequacy of self-collected vaginal fluid Gram's stains was validated. Changes in vaginal flora were demonstrated over a 30-day period by use of this methodology.

Effect of concurrent lower genital tract infections on cervical cancer screening.

BACKGROUND AND OBJECTIVES: Although women attending STD clinics are at high risk for cervical cancer, most STD programmes do not include Papanicolaou (Pap) smears in their routine screening procedures. Concerns regarding reliability of this test in a population with a high rate of active infection are often raised. The objective of this study was to analyse the associations between STD diagnosis/clinical syndromes and unsatisfactory and abnormal Pap smears. METHODS: Retrospective analysis of Pap results and medical records from women attending an inner city STD programme. RESULTS: Of the 1202 patients analysed, 3.2% had squamous intraepithelial lesions (SIL) and 3.5% had smears which were unsatisfactory because of the thickness of the specimen. There were no associations between STD diagnoses and SIL; however, the presence of cervical inflammation was significantly associated with SIL. Pap smears which were unsatisfactory because they were too thick were also associated with the clinical finding of cervical inflammation. CONCLUSIONS: The presence of active infection did not preclude the detection of SIL on Pap smears. The percentage of unsatisfactory smears resulting from inflammation was low.

Tuberculosis screening in a sexually transmitted diseases clinic.

BACKGROUND AND OBJECTIVES: Patients attending sexually transmitted diseases (STD) clinics may be at high risk for tuberculosis (TB) infection. The authors conducted a pilot study of TB screening in this setting to determine the prevalence of TB infection and compliance of the population with a screening program. GOALS: To determine the prevalence of positive skin test results indicating TB among patients attending an STD clinic and to test a simple incentive designed to enhance compliance with return visits for skin test interpretation. STUDY DESIGN: Skin tests for TB were offered to clients attending an STD clinic. Testing was accompanied by self-assessment questionnaires designed to assess risk for TB. After 2 months, a simple incentive package was initiated to enhance compliance with skin test interpretation. RESULTS: The prevalence of positive skin test results was 34%. Compliance with return visits was doubled by use of the simple incentive package. CONCLUSIONS: Patients attending STD clinics are at high risk for TB and can be motivated toward increased compliance by the use of simple incentives.

Metronidazole: utilization in the obstetric and gynecologic patient.

BACKGROUND: Obstetric and gynecologic complications associated with bacterial vaginosis and trichomoniasis have heightened awareness of these conditions, and thus metronidazole's role in obstetric and gynecologic practice continues to increase. GOAL OF THIS STUDY: To review the clinical indications for metronidazole in the obstetric and gynecologic setting, as well as the pharmacokinetics and potential adverse effects of the drug. STUDY DESIGN: Review of the current literature concerning metronidazole. RESULTS AND CONCLUSIONS: Metronidazole remains a valuable agent for the treatment of anaerobic and protozoal infections with little evidence of resistance. Although issues of mutagenicity and carcinogenicity remain theoretical concerns, current data do not support the existence of these risks in humans.

Evaluation of Syva's enzyme immunoassay for the detection of Chlamydia trachomatis in urogenital specimens.

A newly developed microwell enzyme immunosorbent assay (EIA) system by Syva Company (Palo Alto, CA) can detect Chlamydia trachomatis in < 3 hr. It uses a polyclonal antibody to chlamydial lipopolysaccharide and end points are determined with a spectrophotometer. Three clinical trial sites (University of California Medical Center, San Francisco, CA; University of Washington, Seattle, WA; and Louisiana State University Medical Center, New Orleans, LA), compared this EIA with tissue culture (TC) for identifying Chlamydia in urogenital specimens. Overall prevalence by TC was 10.4% (136 of 1306). When tests were compared with TC (using vials or microtiter plates and a fluorescent antibody stain), we found an EIA sensitivity of 93.4% (127 of 136) and a specificity of 98.1% (1148 of 1170). This EIA has a performance profile that is, at the very least, comparable with other nonculture methods for diagnosing genital tract infections with C. trachomatis.

Use of a urine enzyme immunoassay as a diagnostic tool for Chlamydia trachomatis urethritis in men.

We collected first-voided urine specimens from 659 males attending a sexually transmitted disease clinic and performed both enzyme immunoassay (EIA) for detection of chlamydial antigen and leukocyte esterase testing on these urine samples. The overall prevalence of chlamydial urethritis in the study population as determined by culture of urethral swabs was 11%. However, 46% of all men in the study had no symptoms of urethritis. Compared with urethral cultures for chlamydiae, the urine EIA had a sensitivity of 42% and a specificity of 99%. The sensitivity of the EIA strongly correlated with the amount of antigen present in culture as assessed by numbers of inclusion-forming units. The sensitivity of the leukocyte esterase test compared with that of chlamydia culture was 88%. We conclude that in this population of men, which included many patients without symptoms of urethritis, the urine EIA was a relatively insensitive means of screening for chlamydial infection.

Use of sequential enzyme immunoassay and direct fluorescent antibody tests for detection of Chlamydia trachomatis infections in women.

Endocervical infections due to Chlamydia trachomatis remain difficult to diagnose due to the lack of an inexpensive, rapid, and accurate test. We evaluated an alternative strategy for diagnosis in which initial screening was performed with an enzyme immunoassay (Chlamydiazyme) followed by a direct fluorescent antibody (DFA) test on specimens in which the Chlamydiazyme optical density (OD) reading fell in an intermediate zone. Lowering the Chlamydiazme OD ratio (specimen to control) used to define a positive test from 1.0 (the ratio suggested by the manufacturer) to 0.3 raised the sensitivity of Chlamydiazyme from 73 to 83%. Confirmation of those specimens having OD ratios of 0.3 to 0.99 by DFA testing increased the specificity of Chlamydiazyme from 95 to 100%. This strategy necessitated performance of the DFA test on 5% of the specimens. Lowering the cutoff OD ratio below 0.3 increased the sensitivity even further but required DFA testing on greater than 25% of the specimens. Use of an adjusted positive cutoff value for defining positive enzyme immunoassays followed by DFA confirmation for intermediate-zone readings may be a feasible approach for some laboratories that lack cell culture facilities.

Pneumonia due to Legionella micdadei in bone marrow transplant recipients.

Legionella micdadei has previously been described as a cause of nosocomial pneumonia, particularly in kidney transplant recipients. Cell-mediated immunity is the principal host defense against this pathogen. A common clinical scenario in the immunocompromised host is that of septic pulmonary embolus, but asymptomatic infections have also been reported. The organism is weakly acid-fast in clinical specimens but loses this property when grown on solid media. We report two cases of L. micdadei pneumonia, differing markedly in clinical severity and outcome, in bone marrow transplant recipients. Additionally, we note the growth of the organism in liquid culture media with preservation of its acid-fast property.