Randomized Multicenter Trial for the Validation of an Easy-to-Administer Algorithm to Define Penicillin Allergy Status in Sexually Transmitted Infection Clinic Outpatients.

BACKGROUND: Approximately 15% of patients in sexually transmitted infection (STI) clinics report penicillin allergies, complicating treatment for syphilis and gonorrhea. Nonetheless, >90% do not have a penicillin allergy when evaluated. We developed and validated an algorithm to define which patients reporting penicillin allergy can be safely treated at STI clinics with these drugs. METHODS: Randomized controlled trial to assess feasibility and safety of penicillin allergy evaluations in STI clinics. Participants with reported penicillin allergy answered an expert-developed questionnaire to stratify risk. Low-risk participants underwent penicillin skin testing (PST) followed by amoxicillin 250 mg challenge or a graded oral challenge (GOC)-amoxicillin 25 mg followed by 250 mg. Reactions were recorded, and participant/provider surveys were conducted. RESULTS: Of 284 participants, 72 (25.3%) were deemed high risk and were excluded. Of 206 low-risk participants, 102 (49.5%) underwent PST without reactions and 3 (3%) had mild reactions during the oral challenge. Of 104 (50.5%) participants in the GOC, 95 (91.3%) completed challenges without reaction, 4 (4.2%) had mild symptoms after 25 mg, and 4 (4.2%) after 250-mg doses. Overall, 195 participants (94.7%) successfully completed the study and 11 (5.3%) experienced mild symptoms. Of 14 providers, 12 (85.7%) completed surveys and 11 (93%) agreed on the safety/effectiveness of penicillin allergy assessment in STI clinics. CONCLUSIONS: An easy-to-administer risk-assessment questionnaire can safely identify patients for penicillin allergy evaluation in STI clinics by PST or GOC, with GOC showing operational feasibility. Using this approach, 67% of participants with reported penicillin allergy could safely receive first-line treatments for gonorrhea or syphilis. Clinical Trials Registration. Clinicaltrials.gov (NCT04620746).

Clinical Evaluation of a New Molecular Test for the Detection of Organisms Causing Vaginitis and Vaginosis.

In this prospective, observational, method comparison clinical study, the Xpert Xpress MVP test (MVP) was evaluated using both clinician-collected (CVS) and self-collected vaginal swabs (SVS) collected in a clinical setting. The study was conducted at 12 sites, including point-of-care (POC) settings, from geographically diverse locations in the United States. Participants were biologically female patients ≥ 14 years old with signs and/or symptoms of vaginitis/vaginosis. MVP test results for BV were compared to the BD MAX Vaginal Panel (BDVP). Results for Candida group and Candida glabrata and Candida krusei targets (species not differentiated) were assessed relative to yeast culture followed by mass spectrometry for species identification. Trichomonas vaginalis (TV) results were compared relative to a composite method that included results from the BDVP and InPouch TV culture. The investigational test demonstrated high positive percent agreement ranging from 93.6 to 99.0%, and negative percent agreement ranging from 92.1% to 99.8% for both CVS and SVS specimens, indicating it may be a valuable tool for the diagnosis of vaginitis/vaginosis in laboratory and POC settings.

A Comparison of Single-Dose Versus Multidose Metronidazole by Select Clinical Factors for the Treatment of Trichomonas vaginalis in Women.

BACKGROUND: In a randomized controlled trial of 2 g (single-dose) metronidazole (MTZ) versus 500 mg twice daily for 7 days (multidose) for Trichomonas vaginalis treatment, multidose was superior. We examined if the effect was similar by select clinical factors to determine if treatment recommendations could be targeted. METHODS: The primary outcome was T. vaginalis repeat infection at test-of-cure (TOC) 4 weeks after completion of therapy. Analyses were stratified by T. vaginalis history, baseline genital symptoms, and concurrent diagnosis of bacterial vaginosis (BV) per Nugent score at baseline. RESULTS: Women who returned for TOC (n = 540) were included. At baseline, 52.9% had a self-reported history of T. vaginalis; 79.3%, genital symptoms; 5.8%, a gonorrhea diagnosis; and 47.5%, BV. During follow-up, 97.4% took all MTZ as instructed and 34.5% had interval condomless sex with a baseline partner. At TOC, 14.8% tested positive for T. vaginalis. In stratified analysis, women randomized to single-dose MTZ had a higher rate of TOC T. vaginalis positivity than those randomized to multidose if they were symptomatic at baseline (21.4% vs. 10.8%, P = 0.003) or had a reported history of T. vaginalis (24.1% vs. 12.6%, P = 0.01). Test-of-cure T. vaginalis positivity was higher for women receiving a single dose (18.9%) versus multidose (10.8%), irrespective of baseline BV status (P > 0.06). In multivariable analysis, only a history of T. vaginalis and single-dose MTZ were independently associated with a positive TOC for T. vaginalis. CONCLUSIONS: Although multidose MTZ is recommended for all women with T. vaginalis, it is especially important for women with a T. vaginalis history and, given high posttreatment infection rates, a TOC should be performed.

Characteristics of Mycoplasma genitalium Urogenital Infections in a Diverse Patient Sample from the United States: Results from the Aptima Mycoplasma genitalium Evaluation Study (AMES).

Data from a large prospective multicenter clinical validation study of a nucleic acid amplification in vitro diagnostic test for Mycoplasma genitalium were analyzed to describe the prevalence of M. genitalium infection, risk factors, and disease associations in female and male patients seeking care in diverse geographic regions of the United States. Among 1,737 female and 1,563 male participants, the overall prevalence of M. genitalium infection was 10.3% and was significantly higher in persons ages 15 to 24 years than in persons ages 35 to 39 years (for females, 19.8% versus 4.7% [odds ratio {OR} = 5.05; 95% confidence interval {CI} = 3.01 to 8.46]; for males, 16.5% versus 9.4% [OR = 1.91; 95% CI = 1.20 to 3.02]). The risk for M. genitalium infection was higher in black than in white participants (for females, 12.0% versus 6.8% [OR = 1.88; 95% CI = 1.30 to 2.72]; for males, 12.9% versus 6.9% [OR = 2.02; 95% CI = 1.38 to 2.96]) and higher in non-Hispanic than in Hispanic participants (for females, 11.2% versus 6.0% [OR = 1.97; 95% CI = 1.25 to 3.10]; for males, 11.6% versus 6.8% [OR = 1.80; 95% CI = 1.14 to 2.85]). Participants reporting urogenital symptoms had a significantly elevated risk of M. genitalium infection compared to that for asymptomatic individuals (for females, OR = 1.53 [95% CI = 1.09 to 2.14]; for males, OR = 1.42 [95% CI = 1.02 to 1.99]). Women diagnosed with vaginitis and cervicitis had a higher prevalence of M. genitalium infection than women without those diagnoses, although this was statistically significant only for vaginitis (for vaginitis, OR = 1.88 [95% CI = 1.37 to 2.58]; for cervicitis, OR = 1.42 [95% CI = 0.61 to 2.96]). A diagnosis of urethritis in men was also significantly associated with M. genitalium infection (OR = 2.97; 95% CI = 2.14 to 4.13). Few characteristics distinguished asymptomatic from symptomatic M. genitalium infections. These results from persons seeking care in the United States suggest that M. genitalium infection should be considered in young persons presenting with urogenital symptoms.

Mycoplasma genitalium Infections in Women Attending a Sexually Transmitted Disease Clinic in New Orleans.

BACKGROUND: Mycoplasma genitalium has been significantly and nonsignificantly associated with cervicitis, urethritis, or vaginal discharge. This study examined the associations of M. genitalium with selected sexually transmitted infections (STIs) and demographic, behavioral, and clinical factors among women attending a sexually transmitted disease (STD) clinic in New Orleans. METHODS: Women aged ≥18 years who presented to the New Orleans STD clinic provided sociodemographic data and sexual behavior; STI, obstetric, and gynecologic history; and urine, vaginal, endocervical, and rectal specimens. Specimens were tested for M. genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma hominis, Ureaplasma species, and yeast. Bacterial vaginosis (BV) was diagnosed by Nugent score, and cervicitis was defined as ≥30 polymorphonuclear leukocytes per high-power microscopic field on a cervical Gram stain or yellow mucopus on an endocervical swab. RESULTS: Among 400 women studied, M. genitalium was independently significantly associated with age <25 years (P < .03) and with ≥2 sexual partners in the last 12 months (P < .003). Neisseria gonorrhoeae (adjusted odds ratio [AOR], 1.75; P = .103), C. trachomatis (AOR, 1.43; P = .247), and T. vaginalis (AOR, 1.60; P = .120) independently increased the odds of infection with M. genitalium. Controlling for other STIs and BV, there was a positive trend for M. genitalium to predict cervicitis (AOR, 3.18 [95% confidence interval, .99-10.2]; P = .05). CONCLUSIONS: Mycoplasma genitalium in our study displayed the clinical features of C. trachomatis and N. gonorrhoeae, the 2 organisms that drive research agendas in diagnosis, treatment, and prevention of bacterial STIs.

Molecular Testing for Mycoplasma genitalium in the United States: Results from the AMES Prospective Multicenter Clinical Study.

A prospective multicenter clinical study involving subjects from 21 sites across the United States was conducted to validate the performance of a new in vitro diagnostic nucleic acid amplification test (NAAT) for the detection of Mycoplasma genitalium Seven urogenital specimen types (n = 11,556) obtained from 1,778 females, aged 15 to 74 years, and 1,583 males, aged 16 to 82 years, were tested with the Aptima Mycoplasma genitalium assay, an investigational transcription-mediated amplification (TMA) NAAT for the detection of M. genitalium 16S rRNA. Infected status for enrolled subjects was established using results obtained from testing either self-collected vaginal swab or clinician-collected male urethral swab specimens with a composite reference method consisting of three transcription-mediated amplification NAATs targeting unique regions of M. genitalium 16S or 23S rRNA. M. genitalium prevalence was 10.2% in females and 10.6% in males; prevalence was high in both symptomatic and asymptomatic subjects for both sexes. Compared to the subject infected status standard, the investigational test had sensitivity and specificity estimates, respectively, of 98.9% and 98.5% for subject-collected vaginal swabs, 92.0% and 98.0% for clinician-collected vaginal swabs, 81.5% and 98.3% for endocervical swabs, 77.8% and 99.0% for female urine, and 98.2% and 99.6% for male urethral swabs, 88.4% and 97.8% for self-collected penile meatal swabs, and 90.9% and 99.4% for male urine specimens. For all seven specimen types, within-specimen positive and negative agreements between the investigational test and the composite reference standard ranged from 94.2% to 98.3% and from 98.5 to 99.9%, respectively. These results provide clinical efficacy evidence for the first FDA-cleared NAAT for M. genitalium detection in the United States.

Detection of Chlamydia trachomatis and Neisseria gonorrhoeae with the cobas CT/NG v2.0 test: performance compared with the BD ProbeTec CT Qx and GC Qx amplified DNA and Aptima AC2 assays.

OBJECTIVES: Infections due to Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are among the most common bacterial sexually transmitted infections worldwide, most of which are asymptomatic. Detection of infection using a variety of specimen types in symptomatic and asymptomatic subjects is important to effectively combat CT/NG infections. The performance of the cobas CT/NG v2.0 test was assessed for urogenital swabs, urine and cervical cytology samples collected in PreservCyt Solution from 5266 symptomatic and asymptomatic women (including 202 who were pregnant), and urine from 738 men. METHODS: Sensitivity and specificity were estimated compared with a patient infected status determined using two US Food and Drug Administration-cleared nucleic acid amplification tests. RESULTS: Among 6004 participants, 487 CT (8.1%) and 159 NG (2.6%) infections were identified. Sensitivity estimates for CT for women ranged from 91.2% to 97.6% depending on specimen type, and the estimate for male urine specimens was 98.4%. Specificity for CT ranged from 99.2% to 99.7%. Sensitivity estimates for NG ranged from 95.6% to 100.0% for women, and the estimate for men was 100.0%. Specificity for NG ranged from 99.3% to 100.0%. CONCLUSIONS: The cobas CT/NG v2.0 test performs well using urogenital swabs, urine and cervical samples collected in PreservCyt solution.

Phenytoin-Induced Purple Glove Syndrome: A Case Report and Review of the Literature.

OBJECTIVE: To present a case report and literature review of phenytoin-induced purple glove syndrome (PGS). CASE SUMMARY: A 54-year-old African American male presented to our hospital's emergency department (ED) following a seizure episode, cardiac arrest, and loss of consciousness. On arrival to the ED, the patient's total phenytoin level was subtherapeutic at 4.1 mcg/mL and his corrected total phenytoin level was subtherapeutic at 5.1 mcg/mL. In the ED, the patient received a loading dose of intravenous (IV) phenytoin 1,000 mg once via the left cephalic vein, at a rate of 50 mg/min, and was admitted to the medicine service. A day following IV phenytoin administration, a nurse noticed an IV fluid infiltration on the skin tissue around the left cephalic vein. The area appeared dark blue and purple in color, swollen, erythematous, and warm to touch. An ultrasound of the left upper extremity was performed and revealed subcutaneous fluid collection without evidence of thrombosis. DISCUSSION: The Naranjo Adverse Drug Reaction Probability Scale assigned a score of 7, indicating phenytoin as the probable cause of purple glove syndrome (PGS). The patient's PGS was managed with a combination of dry dressing material, left forearm elevation, collagenase topical cream, 0.1% IV bupivacaine, and IV fentanyl. The patient's injury was resolving at the time of discharge to a rehabilitation facility. CONCLUSION: PGS is a rare complication of IV phenytoin therapy. The risk of PGS for this patient may have been abated by decreasing the phenytoin infusion rate from 50 mg/min to less than 25 mg/min.

Unique vaginal microbiota that includes an unknown Mycoplasma-like organism is associated with Trichomonas vaginalis infection.

BACKGROUND: The prevalence of Trichomonas vaginalis infection is highest in women with intermediate Nugent scores. We hypothesized that the vaginal microbiota in T. vaginalis-infected women differs from that in T. vaginalis-uninfected women. METHODS: Vaginal samples from 30 T. vaginalis-infected women were matched by Nugent score to those from 30 T. vaginalis-uninfected women. Equal numbers of women with Nugent scores categorized as normal, intermediate, and bacterial vaginosis were included. The vaginal microbiota was assessed using 454 pyrosequencing analysis of polymerase chain reaction-amplified 16S ribosomal RNA gene sequences. The 16S ribosomal RNA gene sequence of an unknown organism was obtained by universal bacterial polymerase chain reaction amplification, cloning, and sequencing. RESULTS: Principal coordinates analysis of the pyrosequencing data showed divergence of the vaginal microbiota in T. vaginalis-infected and T. vaginalis-uninfected patients among women with normal and those with intermediate Nugent scores but not among women with bacterial vaginosis. Cluster analysis revealed 2 unique groups of T. vaginalis-infected women. One had high abundance of Mycoplasma hominis and other had high abundance of an unknown Mycoplasma species. Women in the former group had clinical evidence of enhanced vaginal inflammation. CONCLUSIONS: T. vaginalis may alter the vaginal microbiota in a manner that is favorable to its survival and/or transmissibility. An unknown Mycoplasma species plays a role in some of these transformations. In other cases, these changes may result in a heightened host inflammatory response.

Client Perspectives on the Development of a Rapid PrEP Initiative at a Sexual Health Center in New Orleans, Louisiana.

Uptake of PrEP remains suboptimal, especially in the Southern United States. Same-day or "Rapid PrEP Initiatives" (RPIs) in sexual health centers (SHCs) could facilitate access and overcome barriers to PrEP. We studied the adaptation of an RPI from Denver, Colorado to an SHC in New Orleans, Louisiana. Through focus group discussions (FGDs) with local SHC staff and PrEP providers, we developed a preliminary RPI model. In 5 FGDs with SHC clients referred for or taking PrEP, we gathered adaptation recommendations and feedback on model acceptability, feasibility, and utility. Providers and clients voiced unanimous support for the RPI. Clients favored the ease of same-day PrEP initiation and emphasized a desire for navigational support, financial counseling, and integration of PrEP care with their other clinical needs. Clients recommended that SHC providers discuss PrEP and HIV with all patients, regardless of providers' perception of risk. Next steps include small-scale implementation and evaluation.

Client Perspectives on the Development of a Same-Day PrEP Initiation Protocol at a Sexual Health Center in New Orleans, LouisianaUptake of PrEP remains low, especially in the Southern United States. Same-day or "Rapid PrEP Initiatives" (RPIs) in sexual health centers (SHCs) could facilitate access and overcome barriers to PrEP. RPIs provide eligible clients with an opportunity to start PrEP on the same day they receive screening for sexually transmitted infections. We studied the adaptation of an RPI from Denver, Colorado, to an SHC in New Orleans, Louisiana. Through focus group discussions (FGDs) with local SHC staff and PrEP providers, we developed a preliminary RPI model. In five FGDs with SHC clients referred for or taking PrEP, we gathered adaptation recommendations and feedback on RPI model acceptability, feasibility, and utility. Providers and clients voiced unanimous support for the RPI. Clients favored the ease of same-day PrEP initiation and emphasized a desire for navigational support, financial counseling, and integration of PrEP care with their other clinical needs. Clients recommended that SHC providers discuss PrEP and HIV with all patients, regardless of providers' perception of risk. Next steps include small-scale implementation and evaluation.

Characteristics of Mpox Infections in Louisiana in the 2022 Outbreak.

The 2022 outbreak of mpox in Louisiana was limited to just >300 cases, perhaps an unexpected outcome given the state's high rates of HIV and other sexually transmitted infections (STIs). We aimed to describe the local outbreak within two health centers in the New Orleans region, partnering with the Louisiana Department of Health to offer additional statewide data. We reviewed charts of persons testing positive for mpox in New Orleans from July to November 2022 at two local health centers that together accounted for half of local cases. We abstracted data on HIV status, immune function [CD4 count, viral load (VL)], antiretroviral therapy regimen, symptoms and severity of infection, vaccination status, and whether tecovirimat was administered. We present local data relative to statewide data (July 2022-January 2023). Of 103 individuals in our network for whom charts were reviewed, 96 (93%) identified as male, 52 (50%) were Black, and 69 (67%) had HIV, including 12 (17%) with uncontrolled HIV (CD4 < 200 cells/mm3 or VL >200 copies/mL). The most common presenting symptoms were rash (n = 71, 69%), fever (n = 36, 35%), and rectal pain (n = 33, 32%). Of six (6%) patients hospitalized, four (67%) were persons with HIV (PWH). Two were hospitalized for severe mpox infection with >100 lesions at presentation; both were PWH, and one had uncontrolled infection. Across the state, 307 cases have been identified and 24 have been hospitalized. Of those hospitalized, 18 (75%) were PWH, including 9 (50%) with uncontrolled HIV. The demographic data from Louisiana, a state with high prevalence of STIs and HIV/AIDS, are consistent with prior reports describing the 2022 mpox outbreak. Our results contribute to accumulating data on the severity of infection in individuals with HIV-related immunocompromise.

A novel Gardnerella, Prevotella, and Lactobacillus standard that improves accuracy in quantifying bacterial burden in vaginal microbial communities.

Bacterial vaginosis (BV) is the most common vaginal dysbiosis. In this condition, a polymicrobial biofilm develops on vaginal epithelial cells. Accurately quantifying the bacterial burden of the BV biofilm is necessary to further our understanding of BV pathogenesis. Historically, the standard for calculating total bacterial burden of the BV biofilm has been based on quantifying Escherichia coli 16S rRNA gene copy number. However, E. coli is improper for measuring the bacterial burden of this unique micro-environment. Here, we propose a novel qPCR standard to quantify bacterial burden in vaginal microbial communities, from an optimal state to a mature BV biofilm. These standards consist of different combinations of vaginal bacteria including three common BV-associated bacteria (BVAB) Gardnerella spp. (G), Prevotella spp. (P), and Fannyhessea spp. (F) and commensal Lactobacillus spp. (L) using the 16S rRNA gene (G:P:F:L, G:P:F, G:P:L and 1G:9L). We compared these standards to the traditional E. coli (E) reference standard using known quantities of mock vaginal communities and 16 vaginal samples from women. The E standard significantly underestimated the copy numbers of the mock communities, and this underestimation was significantly greater at lower copy numbers of these communities. The G:P:L standard was the most accurate across all mock communities and when compared to other mixed vaginal standards. Mixed vaginal standards were further validated with vaginal samples. This new G:P:L standard can be used in BV pathogenesis research to enhance reproducibility and reliability in quantitative measurements of BVAB, spanning from the optimal to non-optimal (including BV) vaginal microbiota.

Association of Chlamydia trachomatis burden with the vaginal microbiota, bacterial vaginosis, and metronidazole treatment.

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming units (IFU) and Ct genome copy number (GCN), and 16S rRNA gene sequencing was used to determine the composition of the vaginal microbiota. We observed a six-log spectrum of IFU and an eight-log spectrum of GCN in our study participants at their enrollment visit, but BV, as indicated by Amsel's criteria, Nugent scoring, or VALENCIA community state typing, did not predict infectious and total Ct burden, although IFU : GCN increased with Amsel and Nugent scores and in BV-like community state types. Ct burden was, however, associated with the abundance of bacterial species in the vaginal microbiota, negatively with Lactobacillus crispatus and positively with Prevotella bivia. Women diagnosed with BV were treated with metronidazole, and Ct burden was significantly reduced in those who resolved BV with treatment. A subset of women naturally cleared Ct infection in the interim, typified by low Ct burden at enrollment and resolution of BV. Abundance of many BVAB decreased, and Lactobacillus increased, in response to metronidazole treatment, but no changes in abundances of specific vaginal bacteria were unique to women who spontaneously cleared Ct infection.

Performance of the cobas CT/NG test compared to the Aptima AC2 and Viper CTQ/GCQ assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae.

The next-generation amplification test for Chlamydia trachomatis and Neisseria gonorrhoeae (Roche cobas 4800), a fully automated system, was compared head to head, using female samples, to Gen-Probe Aptima Combo 2 and BD ProbeTec using Viper. Endocervical swabs, female urine, and endocervical samples in liquid-based cytology medium were run on at least two of three platforms. A total of 4,316 samples were evaluated, and 281 chlamydial and 69 gonococcal infections were identified. Estimates of sensitivity and specificity were obtained relative to the patient infection standard (PIS) and using latent class analysis (LCA). Chlamydia sensitivity estimates ranged from 86.9 to 95.6% using PIS and 97.6 to 98% using LCA. Specificity was ≥ 99.6% for all sample types. Sensitivity ranged from 95.6 to 100% using PIS and 96.9 to 100% using LCA for the detection of gonococcal infections. Specificity for gonococcal infections was ≥ 99.8%. cobas 4800 performance was equivalent to the comparator assays (all P values, >0.05), and the fully automated system provides high laboratory efficiency.

Evaluation of the Roche cobas® CT/NG test for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in male urine.

BACKGROUND: The Roche cobas® CT/NG test (c4800), performed on the cobas 4800 system, is a new diagnostic assay using an automated workstation to isolate nucleic acids from clinical specimens and a real-time instrument for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). This study compared the performance characteristics of the c4800 with the Becton Dickinson ProbeTec™ CT/GC Q(x) assay (Q(x)) and Gen-Probe® Aptima Combo 2 (AC2) assay for the detection of CT and NG in male urine using patient-infected-status (PIS). METHODS: Urine and urethral swabs were obtained from men attending STD, family planning, or OB/GYN clinics from 11 geographically distinct locations. Aliquot order was randomized for urine specimens between AC2, c4800, and Q(x). Urethral swabs were randomized between AC2 and Q(x). Urethral swabs were only used to define PIS and were not tested on the c4800. A participant was considered infected if the 2 comparator assays with different molecular targets had positive results from either sample type. RESULTS: A total of 790 men were screened, with 768 evaluable for CT and NG. Symptoms were reported in 296 (38.5%) participants. For urine, the overall sensitivity and specificity of the c4800 assay for CT were 97.6% and 99.5%, respectively, when compared with PIS. Sensitivity and specificity for NG were 100% and 99.7%, respectively. CONCLUSIONS: The c4800 has excellent sensitivity and specificity for male urine specimens when compared with PIS. Assay performance was similar in symptomatic and asymptomatic men and was equivalent to nucleic acid amplification tests that are currently on the market.

Utility of urine, vaginal, cervical, and rectal specimens for detection of Mycoplasma genitalium in women.

This study assessed the utility of urine, vaginal, cervical, and rectal specimens for the detection of Mycoplasma genitalium in women by using our laboratory-developed PCR assay. The relative sensitivity was 85.7% for the vaginal swab specimen, 74.3% for the endocervical swab specimen, 61.4% for the urine specimen, and 24.3% for the rectal swab specimen.

Human genital antibody-mediated inhibition of Chlamydia trachomatis infection and evidence for ompA genotype-specific neutralization.

The endocervix, the primary site of Chlamydia trachomatis (Ct) infection in women, has a unique repertoire of locally synthesized IgG and secretory IgA (SIgA) with contributions from serum IgG. Here, we assessed the ability of genital and serum-derived IgG and IgA from women with a recent positive Ct test to neutralize Ct elementary bodies (EBs) and inhibit inclusion formation in vitro in human endocervical epithelial cells. We also determined if neutralization was influenced by the major outer membrane protein (MOMP) of the infecting strain, as indicated by ompA gene sequencing and genotyping. At equivalent low concentrations of Ct EB (D/UW-3/Cx + E/UW-5/Cx)-specific antibody, genital-derived IgG and IgA and serum IgA, but not serum IgG, significantly inhibited inclusion formation, with genital IgA being most effective, followed by genital IgG, then serum IgA. The well-characterized Ct genotype D strain, D/UW-3/Cx, was neutralized by serum-derived IgG from patients infected with genotype D strains, genital IgG from patients infected with genotype D or E strains, and by genital IgA from patients infected with genotype D, E, or F strains. Additionally, inhibition of D/UW-3/Cx infection by whole serum, rather than purified immunoglobulin, was associated with levels of serum EB-specific IgG rather than the genotype of infecting strain. In contrast, a Ct genotype Ia clinical isolate, Ia/LSU-56/Cx, was neutralized by whole serum in a genotype and genogroup-specific manner, and inhibition also correlated with EB-specific IgG concentrations in serum. Taken together, these data suggest that (i) genital IgA most effectively inhibits Ct infection in vitro, (ii) human antibody-mediated inhibition of Ct infection is significantly influenced by the ompA genotype of the infecting strain, (iii) the genital antibody repertoire develops or matures differently compared to systemic antibody, and (iv) ompA genotype-specificity of inhibition of infection by whole serum can be overcome by high concentrations of Ct-specific IgG.

Differences in the Genital Microbiota in Women Who Naturally Clear Chlamydia trachomatis Infection Compared to Women Who Do Not Clear; A Pilot Study.

In vitro studies indicate IFNγ is central to Chlamydia trachomatis (Ct) eradication, but its function may be compromised by anaerobes typically associated with bacterial vaginosis (BV), a frequent co-morbidity in women with Ct. Here we investigated the associations between natural clearance of cervical Ct infection, the vaginal microbiome, and the requirements for IFNγ by evaluating the vaginal microbial and cytokine composition of Ct treatment visit samples from women who cleared Ct infection in the interim between their Ct screening and Ct treatment visit. The pilot cohort was young, predominantly African American, and characterized by a high rate of BV that was treated with metronidazole at the Ct screening visit. The rate of natural Ct clearance was 23.6% by the Ct treatment visit (median 9 days). 16S rRNA gene sequencing revealed that metronidazole-treated women who had a Lactobacillus spp.-dominant vaginal microbiota (CST 2 or 3) at the Ct treatment visit, were more prevalent in the Ct clearing population than the non-clearing population (86% v. 50%). L. iners (CST2) was the major Lactobacillus spp. present in Ct clearers, and 33% still remained anaerobe-dominant (CST1). Vaginal IFNγ levels were not significantly different in Ct clearers and non-clearers and were several logs lower than that required for killing Ct in vitro. An expanded panel of IFNγ-induced and proinflammatory cytokines and chemokines also did not reveal differences between Ct clearers and non-clearers, but, rather, suggested signatures better associated with specific CSTs. Taken together, these findings suggest that BV-associated bacteria may impede Ct clearance, but a Lactobacillus spp.-dominant microbiome is not an absolute requirement to clear. Further, IFNγ may be required at lower concentrations than in vitro modeling indicates, suggesting it may act together with other factors in vivo. Data also revealed that the vaginal bacteria-driven inflammation add complexity to the genital cytokine milieu, but changes in this microbiota may contribute to, or provide cytokine biomarkers, for a shift to Ct clearance.

Single-dose versus 7-day-dose metronidazole for the treatment of trichomoniasis in women: an open-label, randomised controlled trial.

BACKGROUND: Among women, trichomoniasis is the most common non-viral sexually transmitted infection worldwide, and is associated with serious reproductive morbidity, poor birth outcomes, and amplified HIV transmission. Single-dose metronidazole is the first-line treatment for trichomoniasis. However, bacterial vaginosis can alter treatment efficacy in HIV-infected women, and single-dose metronidazole treatment might not always clear infection. We compared single-dose metronidazole with a 7-day dose for the treatment of trichomoniasis among HIV-uninfected, non-pregnant women and tested whether efficacy was modified by bacterial vaginosis. METHODS: In this multicentre, open-label, randomised controlled trial, participants were recruited at three sexual health clinics in the USA. We included women positive for Trichomonas vaginalis infection according to clinical screening. Participants were randomly assigned (1:1) to receive either a single dose of 2 g of metronidazole (single-dose group) or 500 mg of metronidazole twice daily for 7 days (7-day-dose group). The randomisation was done by blocks of four or six for each site. Patients and investigators were aware of treatment assignment. The primary outcome was T vaginalis infection by intention to treat, at test-of-cure 4 weeks after completion of treatment. The analysis of the primary outcome per nucleic acid amplification test or culture was also stratified by bacterial vaginosis status. This trial is registered with ClinicalTrials.gov, number NCT01018095, and with the US Food and Drug Administration, number IND118276, and is closed to accrual. FINDINGS: Participants were recruited from Oct 6, 2014, to April 26, 2017. Of the 1028 patients assessed for eligibility, 623 women were randomly assigned to treatment groups (311 women in the single-dose group and 312 women in the 7-day-dose group; intention-to-treat population). Although planned enrolment had been 1664 women, the study was stopped early because of funding limitations. Patients in the 7-day-dose group were less likely to be T vaginalis positive at test-of-cure than those in the single-dose group (34 [11%] of 312 vs 58 [19%] of 311, relative risk 0·55, 95% CI 0·34-0·70; p<0·0001). Bacterial vaginosis status had no significant effect on relative risk (p=0·17). Self-reported adherence was 96% in the 7-day-dose group and 99% in the single-dose group. Side-effects were similar by group; the most common side-effect was nausea (124 [23%]), followed by headache (38 [7%]) and vomiting (19 [4%]). INTERPRETATION: The 7-day-dose metronidazole should be the preferred treatment for trichomoniasis among women. FUNDING: National Institutes of Health.