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Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men.

This systematic review and meta-analysis provide support for a nearly 2-fold higher risk for acquiring Trichomonas vaginalis among women with bacterial vaginosis compared with women without bacterial vaginosis. Supplemental digital content is available in the text., Background Bacterial vaginosis (BV) has been associated with an increased risk for acquisition of human immunodeficiency virus and sexually transmitted infections. We evaluated the association between BV and incident Trichomonas vaginalis (TV) infection in women. Methods MEDLINE and ClinicalTrials.gov were searched for articles published between January 1, 1980, and May 7, 2021. Observational studies in women that evaluated the relationship between having/not having BV and the risk for acquiring TV were included. Results Fourteen studies were included in the systematic review; 12 studies were included in meta-analyses involving 18,424 participants. Most studies used Nugent scoring to diagnose BV. For TV diagnosis, 12 studies used wet mount microscopy or culture, and 2 used nucleic acid amplification tests. There was diversity in the measures of association used, so an overall effect size could not be calculated. The majority of studies reported odds ratios, which showed an increased risk of incident TV among women with BV versus without BV (adjusted odds ratio, 1.87; 95% confidence interval, 1.45–2.40; P = 0.007). However, there were heterogeneity and potential confounding factors (eg, age, sexual partners) reported among studies. Conclusions This systematic review and meta-analysis provide evidence for a nearly 2-fold higher risk for acquiring TV among women with BV compared with women without BV.

Background Antimicrobial resistance in Mycoplasma genitalium (MG), a cause of urethritis, is a growing concern. Yet little is known about the geographic distribution of MG resistance in the United States or about its associated clinical outcomes. We evaluated the frequency of MG among men with urethritis, resistance mutations, and posttreatment symptom persistence. Methods We enrolled men presenting with urethritis symptoms to 6 US sexually transmitted disease (STD) clinics during June 2017–July 2018; men with urethritis were eligible for follow-up contact and, if they had persistent symptoms or MG, a chart review. Urethral specimens were tested for MG and other bacterial STDs. Mutations in 23S ribosomal ribonucleic acid (rRNA) loci (macrolide resistance–associated mutations [MRMs]) and in parC and gyrA (quinolone-associated mutations) were detected by targeted amplification/Sanger sequencing. Results Among 914 evaluable participants, 28.7% (95% confidence interval [CI], 23.8–33.6) had MG. Men with MG were more often Black (79.8% vs 66%, respectively), Conclusions MG infection was common among men with urethritis; the MRM prevalence was high among men with MG. Persistent symptoms following treatment were frequent among men both with and without MG.

Background Disease intervention specialists (DIS) provide partner services (PS) for sexually transmitted infections (STI). We assessed an expansion of DIS services for clients with HIV and/or syphilis, and contacts within their social and sexual networks. Methods Black and Latinx cisgender men and transgender women who have sex with men diagnosed with HIV and/or syphilis in four urban North Carolina (NC) counties were referred to designated DIS, who were trained to recruit clients as "seeds" for chain-referral sampling of sociosexual network "peers." All received HIV/STI testing and care; referrals for pre-exposure prophylaxis (PrEP) and social, behavioral, and non-STI medical services were offered. Participants completed baseline, 1 month, and 3 month computerized surveys. Results Of 213 cases referred to DIS from May 2018 to February 2020, 42 seeds (25 with syphilis, 17 with HIV) and 50 peers participated. Median age was 27 years; 93% were Black and 86% were cisgender men. Most peers came from seeds' social networks: 66% were friends, 20% were relatives, and 38% were cisgender women. Incomes were low, 41% were uninsured, and 10% experienced recent homelessness. More seeds than peers had baseline PrEP awareness; attitudes were favorable but utilization was poor. Thirty-seven participants were referred for PrEP 50 times; 17 (46%) accessed PrEP by month 3. Thirty-nine participants received 129 non-PrEP referrals, most commonly for housing assistance, primary care, Medicaid navigation, and food insecurity. Conclusions Chain-referral sampling from PS clients allowed DIS to access persons with significant medical and social service needs, demonstrating that DIS can support marginalized communities beyond STI intervention.

BACKGROUND Adoption of HIV pre-exposure prophylaxis (PrEP) remains limited among populations at greatest risk for HIV acquisition. This study aims to assess awareness of PrEP among individuals in Durham, North Carolina, which has one of the highest rates of HIV diagnoses in the state.METHOD In 2015-2016, we administered a survey including questions to assess PrEP awareness to individuals at multiple venues throughout Durham, North Carolina.RESULTS A total of 139 respondents were surveyed. The majority were male (66%) and black/African American (75%); 21% were Hispanic/Latino. There were an estimated 53 men who have sex with men (MSM), of which 18 (33%) were black MSM M 24 years of age. Overall, only 53/138 (38%) respondents were aware of PrEP. Awareness was reported among 33/52 (63%) MSM respondents, 29/46 (63%) black MSM, and 10/17 (59%) black MSM M 24 years of age. In multivariate analysis, non-heterosexual orientation, health-insured status, and prior HIV testing were significantly associated with PrEP awareness. Ninety-four (69%) of 137 respondents reported prior HIV testing.LIMITATIONS Limitations include non-random sampling and limited sample size. Further research needs to be done in other areas of North Carolina, and assessment of PrEP acceptability and uptake needs to be performed.CONCLUSION This study reveals low overall awareness of PrEP in Durham, North Carolina, indicating that expanded outreach is necessary to increase public awareness and encourage adoption of PrEP among all demographics at risk for HIV.

The syndromic management of genital ulcer disease (GUD) misses asymptomatic syphilis cases but is widely utilized in resource-limited settings without diagnostic capabilities to ensure treatment for the most common etiologies of GUD. We used rapid serology tests for syphilis screening at a Malawian sexually transmitted infections clinic. The estimated seroprevalence was 9% and was highest among patients with genital ulcers (26%) and newly diagnosed HIV infection (19%). Rapid syphilis screening has the potential to increase syphilis detection, but accurate patient histories regarding syphilis diagnosis and prior treatment are needed.

Guidance about integration of comprehensive hepatitis C virus (HCV)-related services in sexually transmitted disease (STD) clinics is limited. We evaluated a federally funded HCV testing and linkage-to-care program at an STD clinic in Durham County, North Carolina. During December 10, 2012, to March 31, 2015, the program tested 733 patients for HCV who reported 1 or more HCV risk factor; 81 (11%) were HCV-infected (ie, HCV antibody-positive and HCV ribonucleic acid-positive). Fifty-one infected patients (63%) were linked to care. We concluded that essential program resources include reflex HCV ribonucleic acid testing; a dedicated bridge counselor to provide test results, health education, and linkage-to-care assistance; and referral relationships for local HCV management and treatment.

Background Mycoplasma genitalium can result in pelvic inflammatory disease and adverse pregnancy outcomes. We analyzed data collected from a prospective study of asymptomatic bacterial vaginosis (BV) to determine the natural history of M. genitalium. Methods Women aged 15-25 years, with asymptomatic BV and ≥2 risk factors for sexually transmitted infection were recruited from 10 sites throughout the United States. Vaginal swab samples were collected at enrollment and through home-based testing every 2 months over 12 months. M. genitalium nucleic acid amplification testing was performed for M. genitalium using transcription-mediated assays (Hologic). The prevalence, incidence, and persistence of M. genitalium, defined as all positive specimens during follow-up, were estimated with 95% confidence intervals (CIs). Adjusted odds ratios (AOR) were calculated using logistic and Poisson regression to evaluate participant characteristics associated with M. genitalium infection. Results Among 1139 women, 233 were M. genitalium positive, for a prevalence of 20.5% (95% CI, 18.2%-22.9%); 42 of 204 had persistent M. genitalium (20.6%). Among 801 M. genitalium-negative women at baseline, the M. genitalium incidence was 36.6 per 100 person-years (95% CI, 32.4-41.3). Black race (AOR, 1.92; 95% CI, 1.09-3.38), age ≤21 years (1.40; 1.03-1.91), and prior pregnancy (1.36; 1.00-1.85) were associated with prevalent M. genitalium; only black race was associated with incident M. genitalium (P = .03). Conclusions We identified high rates of prevalent, incident, and persistent M. genitalium infections among young, high-risk women with asymptomatic BV, supporting the need for clinical trials to evaluate the impact of M. genitalium screening on female reproductive health outcomes.

Expanding access to HIV preexposure prophylaxis (PrEP) could help reduce rates of HIV infection in the United States. This study characterizes activities and barriers to PrEP implementation at local health departments (LHDs) in North Carolina (NC), which contains a large rural population.In May 2016, a web-based survey was distributed to health directors of all county and district health departments in NC to assess PrEP-related activities, perceived barriers to PrEP implementation, and desired PrEP-related resources.Of 85 LHDs in NC, 56 (66%) responded to the survey. Of these, 2 (4%) reported PrEP prescribing and 7 (13%) externally referred for PrEP services. Among the 54 departments not prescribing PrEP, the most frequently cited reasons were cost concerns (n = 25, 46%), lack of formal prescribing protocols (n = 21, 39%), and belief that PrEP would be better managed at primary care or specialty clinics (n = 19, 35%). Among the 47 departments not prescribing or referring clients for PrEP, the most frequently cited reasons for the lack of PrEP referral were the absence of local PrEP providers (n = 29, 62%), lack of PrEP knowledge among staff (n = 13, 28%), and perceived lack of PrEP candidates (n = 12, 26%). The most frequently requested PrEP-related resources included training to help identify PrEP candidates (n = 39, 70%) and training on PrEP prescribing and management (n = 38, 68%).PrEP prescribing and referral among LHDs in NC remains extremely limited. Increased PrEP-related training and support for LHD-based providers could enhance PrEP access, especially in rural and underserved areas.

BACKGROUND Syphilis management is complex and demonstration of treatment response requires monitoring of nontreponemal antibody titers for a ≥ 4-fold decline and/or seroreversion to nonreactive titers. METHODS We evaluated data from a multicenter clinical trial of syphilis treatment conducted from 2000 to 2009 involving human immunodeficiency virus (HIV)-negative patients 18 years or older with early syphilis. To assess the rate of titer decline and seroreversion after effective therapy, rapid plasma reagin (RPR) titers were analyzed at 1, 3, 6, 9, and 12 months among patients with an appropriate treatment response. We plotted the rate of RPR titer decline after treatment, estimated the frequency of seroreversion, and conducted multivariate analyses to assess characteristics associated with seroreversion. RESULTS Among 369 (79.4%) of 465 HIV-negative patients with early syphilis who had an appropriate treatment response, 333 participants had complete RPR data over 12 months. Although the decline in RPR titers was ≥ 4-fold among 88.0% (293/333) of participants at 3 months and ≥ 8-fold among 77.8% at 6 months, only 9.6% achieved complete RPR seroreversion at 6 months and 17.1% at 12 months after therapy. Male sex (adjusted odds ratio, 4.3; 95% confidence interval, 1.8-10.5) and baseline RPR titers ≤ 1:32 (adjusted odds ratio, 14.5; 95% confidence interval, 6.8-31.2) were associated with higher odds of seroreversion compared with females and titers > 1:32, respectively. CONCLUSIONS Despite a ≥ 4-fold RPR titer decline after treatment, the majority of HIV-negative patients with early syphilis failed to have seroreversion at 12 months. Nontreponemal antibody titers often persist despite an appropriate treatment response.

Objective. We evaluated a hepatitis C virus (HCV) testing and linkage-to-care post-release program among detainees of small- to medium-sized jails in North Carolina and South Carolina as part of the Hepatitis Testing and Linkage to Care initiative. Methods. An HCV testing and linkage-to-care program was implemented in selected jails in North Carolina and South Carolina from December 2012 to March 2014. Health-care workers not affiliated with the jails conducted HCV antibody (anti-HCV) and HCV ribonucleic acid (RNA) testing and linkage-to-care activities. The North Carolina jail provided universal opt-out testing for HCV; South Carolina jails initially targeted high-risk individuals before expanding to routine testing. Results. Of 669 detainees tested for HCV in North Carolina, 88 (13.2%) tested anti-HCV positive, of whom 81 (92.0%) received an HCV RNA test, 66 (81.5%) of whom tested HCV RNA positive (i.e., currently infected). Of the 66 detainees with current HCV infection, 18 were referred to HCV medical care post-release and 10 attended their first appointment. Of 224 detainees tested for HCV in South Carolina, 18 (8.0%) tested anti-HCV positive, of whom 13 received an HCV RNA test. Nine of 13 detainees tested HCV RNA positive, seven detainees were referred to post-release medical care, and two detainees attended their first appointment. Overall, 106 of 893 (11.9%) detainees were anti-HCV positive. Conclusion. This study demonstrated that HCV testing, identification of infection, and linkage to care are feasible among jail populations. The rate of anti-HCV positivity was lower than that found in national studies of incarcerated populations, suggesting that HCV infection prevalence in jails may vary across U.S. states or regions.

Antibiotic-resistant Neisseria gonorrhoeae has prompted the development of new therapies. Zoliflodacin is a new antibiotic that inhibits DNA biosynthesis. In this multicenter, phase 2 trial, zoliflodacin was evaluated for the treatment of uncomplicated gonorrhea.We randomly assigned eligible men and women who had signs or symptoms of uncomplicated urogenital gonorrhea or untreated urogenital gonorrhea or who had had sexual contact in the preceding 14 days with a person who had gonorrhea to receive a single oral dose of zoliflodacin (2 g or 3 g) or a single 500-mg intramuscular dose of ceftriaxone in a ratio of approximately 70:70:40. A test of cure occurred within 6±2 days after treatment, followed by a safety visit 31±2 days after treatment. The primary efficacy outcome measure was the proportion of urogenital microbiologic cure in the microbiologic intention-to-treat (micro-ITT) population.From November 2014 through December 2015, a total of 179 participants (167 men and 12 women) were enrolled. Among the 141 participants in the micro-ITT population who could be evaluated, microbiologic cure at urogenital sites was documented in 55 of 57 (96%) who received 2 g of zoliflodacin, 54 of 56 (96%) who received 3 g of zoliflodacin, and 28 of 28 (100%) who received ceftriaxone. All rectal infections were cured in all 5 participants who received 2 g of zoliflodacin and all 7 who received 3 g, and in all 3 participants in the group that received ceftriaxone. Pharyngeal infections were cured in 4 of 8 participants (50%), 9 of 11 participants (82%), and 4 of 4 participants (100%) in the groups that received 2 g of zoliflodacin, 3 g of zoliflodacin, and ceftriaxone, respectively. A total of 84 adverse events were reported: 24 in the group that received 2 g of zoliflodacin, 37 in the group that received 3 g of zoliflodacin, and 23 in the group that received ceftriaxone. According to investigators, a total of 21 adverse events were thought to be related to zoliflodacin, and most such events were gastrointestinal.The majority of uncomplicated urogenital and rectal gonococcal infections were successfully treated with oral zoliflodacin, but this agent was less efficacious in the treatment of pharyngeal infections. (Funded by the National Institutes of Health and Entasis Therapeutics; ClinicalTrials.gov number, NCT02257918 .).

Background To improve the HIV continuum of care, a team of field service interventionists (State Bridge Counselors, SBC) was developed through a state public health system and provided brief (1-2) contacts for linkage of newly diagnosed persons with HIV and reengagement of persons living with HIV (PLWH) who were not in care. Setting North Carolina, United States. Methods Service data from January 2013 to June 2015 were analyzed to determine characteristics of clients referred to SBCs, proportions linked or reengaged in care, and/or achieved viral load suppression (VLs). We evaluated associations between client characteristics and outcomes using multivariable analyses and estimated odds ratios (OR) with 95% confidence intervals (CI). Results SBCs provided linkage services to 299 newly diagnosed individuals and reengagement services to 606 PLWH throughout North Carolina. Among persons who received linkage services, 189 (63%) had evidence of care within 90 days of referral and 205 (69%) had VLs within a year. Among PLWH who received reengagement services, 278 (46%) had care within 90 days and 308 (51%) had VLs within a year. Persons aged 30-39 years (OR, 2.1; 95% CI, 1.1 to 3.9) and 40-49 years had an increased likelihood (OR, 2.4; 95% CI, 1.1 to 5.2) of linkage within 90 days compared with persons aged 18-29 years. Non-white PLWH had an increased OR of 1.7; (95% CI, 1.2 to 2.5) of reengagement compared with whites. Conclusions Our SBC program successfully implemented a "low-touch" approach to provision of linkage and reengagement services, demonstrating that public health resources can be used to address the HIV care continuum on a statewide level.

In this study, we aimed to investigate the performance of nontreponemal antibody tests in cerebrospinal fluid (CSF) specimens from syphilis patients. From September 2009 to September 2012, CSF specimens were collected at the Shanghai Skin Disease Hospital in Shanghai, China, from 1,132 syphilis patients without HIV infection, including 154 with symptomatic and 56 with asymptomatic neurosyphilis. All of the CSF specimens underwent testing with a rapid plasma reagin (RPR) test, an RPR-V (commercial RPR antigen diluted 1:2 in 10% saline) test, the toluidine red unheated serum test (TRUST), and the Venereal Disease Research Laboratory (VDRL) test. Specificities, sensitivities, positive predictive values (PPVs), negative predictive values (NPVs), and kappa values were calculated to determine the performances of the tests. We compared results of the CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST among patients with symptomatic and asymptomatic neurosyphilis who had reactive CSF- Treponema pallidum particle agglutination (TPPA) test results. Overall, the CSF-VDRL test was reactive in 261 patients (23.1%). There were no cases in which the CSF-VDRL was nonreactive and CSF-RPR, CSF-RPR-V, or CSF-TRUST was reactive. Agreement between the results of CSF-TRUST and CSF-RPR was almost perfect (κ = 0.861), with substantial agreement between the results of CSF-RPR and CSF-RPR-V (κ = 0.740). The sensitivities of CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST were 81.4%, 76.2%, 79.5%, and 76.2%, respectively. Compared to CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST had comparable PPVs and NPVs. However, the specificity of CSF-VDRL (90.3%) was significantly lower than those of the other tests (92.7 to 93.4%). Therefore, CSF-RPR, CSF-RPR-V, and CSF-TRUST can be considered alternative tests for neurosyphilis diagnosis in HIV-negative populations, particularly when the CSF-VDRL is not available.

In female sexually transmitted infection clinic attendees, Mycoplasma genitalium was more frequently detected using vaginal (53/73) versus endocervical (43/73) specimens. In women without other sexually transmitted infections, M. genitalium detection (N = 44) was associated with age ≤22 years (odds ratio, 2.53; P = 0.006) and clinical evidence of cervicitis (odds ratio, 2.11; P = 0.03).

Objectives. The national Viral Hepatitis Action Plan recommends strengthening partnerships among health departments, community-based organizations, and health-care providers for hepatitis services. We implemented a hepatitis C virus (HCV) testing and linkage-to-care program through a local health department using similar strategies reported for HIV care. Methods. The Durham County Department of Public Health received federal funding to conduct HCV testing and linkage to care in Durham, North Carolina. HCV antibody testing with reflex RNA was offered through a sexually transmitted disease clinic, a county jail, community testing sites (including a residential substance abuse recovery program), and a homeless clinic. People with evidence of HCV infection were linked to care through an HCV bridge counselor who provided education, incentives, and transportation, and scheduled appointments with HCV specialists at nearby academic centers and on-site clinics. Results. From December 2012 through February 2014, we conducted 2,004 HCV tests, of which 326 (16.3%) were HCV antibody positive and 241 (12.0%) had detectable HCV RNA. Among the 241 people with HCV infection, 178 (73.9%) were men, and 133 (55.2%) were born between 1945 and 1965. Of 241 people with chronic HCV infection, 150 (62.2%) reported ever injecting drugs, eight (2.5%) were coinfected with HIV, and 123 (51.0%) were linked to care. Conclusion. At the local public health level, HCV testing and linkage to care can be facilitated with additional funding and by leveraging existing programs and provider networks to deliver a coordinated system of care.

Objective: An investigation was conducted to determine factors associated with a syphilis outbreak in a rural North Carolina county. Study Design: A retrospective chart review was performed on 61 primary (PS), secondary (SS), and early latent (ELS) syphilis case patients reported in Columbus County between January 2001 and February 2002. Sociosexual network analysis was conducted using electronic contact tracing information. Results: We identified 20 PS, 25 SS, and 16 ELS case patients who were predominantly black. Seventy-two percent had reported ≥1 sexual partner with early syphilis, 51% used crack cocaine and/or had sex with a crack-using partner, and 31% exchanged sex for drugs or money. The sexual network exhibited predominantly linear connections between case patients and sexual partners. Adding social connections to the network further demonstrated dense cyclic interactions characteristic of core groups. Conclusions: The syphilis outbreak in this rural community was associated with crack cocaine and exchange of sex for drugs in a densely interconnected sociosexual network.

Survivors of sexual assault are at risk for acquiring sexually transmitted infections (STIs). We conducted literature reviews and invited experts to assist in updating the sexual assault section for the 2015 Centers for Disease Control and Prevention sexually transmitted diseases (STD) treatment guidelines. New recommendations for STI management among adult and adolescent sexual assault survivors include use of nucleic acid amplification tests (NAATs) for detection of Trichomonas vaginalis by vaginal swabs; NAATs for detection of Neisseria gonorrhoeae and Chlamydia trachomatis from pharyngeal and rectal specimens among patients with a history of exposure or suspected extragenital contact after sexual assault; empiric therapy for gonorrhea, chlamydia, and trichomoniasis based on updated treatment regimens; vaccinations for human papillomavirus (HPV) among previously unvaccinated patients aged 9-26 years; and consideration for human immunodeficiency virus (HIV) nonoccupational postexposure prophylaxis using an algorithm to assess the timing and characteristics of the exposure. For child sexual assault (CSA) survivors, recommendations include targeted diagnostic testing with increased use of NAATs when appropriate; routine follow-up visits within 6 months after the last known sexual abuse; and use of HPV vaccination in accordance with national immunization guidelines as a preventive measure in the post-sexual assault care setting. For CSA patients, NAATs are considered to be acceptable for identification of gonococcal and chlamydial infections from urine samples, but are not recommended for extragenital testing due to the potential detection of nongonococcal Neisseria species. Several research questions were identified regarding the prevalence, detection, and management of STI/HIV infections among adult, adolescent, and pediatric sexual assault survivors.

The Xpert(®) MTB/RIF assay has demonstrated robust capability for diagnosing tuberculosis (TB) and rifampin (RMP) resistance. Optimal use of Xpert in diverse settings will require knowledge of challenges when interpreting the results. We present three selected cases from the United States, a low-burden TB setting, to highlight important clinical scenarios encountered with Xpert testing: rapid RMP resistance detection in a patient with pre-extensively drug-resistant TB who immigrated from the Philippines, false-positive RMP resistance detection, and Mycobacterium tuberculosis detection in a culture-negative patient. These cases demonstrate that a low pre-test probability of TB or drug-resistant TB can complicate the interpretation of the Xpert assay.

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.

The impact of syphilis reverse sequence screening has not been evaluated in community outreach. Using reverse sequence screening in neighborhoods identified with geographic information systems, we found that among 239 participants, 45 (19%) were seropositive. Of these, 3 (7%) had untreated syphilis, 33 (73%) had previously treated syphilis infection, and 9 (20%) had negative nontreponemal test results.

Objectives: Trichomonas vaginalis is the most common nonviral sexually transmitted pathogen. Wet mount microscopy performs poorly compared with culture; however, universal screening using culture would be cost-prohibitive. Goal: The goal of this study was to develop a predictive model for wet mount-negative women who may benefit from targeted use of culture for T. vaginalis detection. Study: Women presenting for sexually transmitted disease evaluation were prospectively screened for trichomoniasis using wet mount and culture. Multivariate logistic regression was used to identify predictors of culture-proven trichomoniasis among wet mount-negative women. Results: A total of 2194 women were screened for trichomoniasis; overall, the prevalence of T. vaginalis was 17.5%. Three predictors (any drug use, contact to trichomoniasis, and African-American race) provided the most specific model (100%); any 1 predictor, the most sensitive model (97.8%). Conclusions: Given the public health impact of trichomoniasis, we recommend using any 1 of 3 predictors to identify women who would benefit from targeted culture for T. vaginalis.

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.

Persistent nontreponemal titers after treatment are common among patients with early syphilis. We retreated 82 human immunodeficiency virus–negative early syphilis participants who were serofast at 6 months using benzathine penicillin. Only 27% exhibited serological response after retreatment and after an additional 6 months of follow-up.

Background Serologic tests for syphilis results at the time of diagnosis are the basis for evaluating response to syphilis therapy. After treatment, however, serologic tests for syphilis titers may continue to increase for several weeks. We evaluated rapid plasma reagin (RPR) titer variation during the 14 days after therapy using data from a recent large, prospective randomized controlled trial. Methods Prospectively enrolled participants in North America and Madagascar 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 posttreatment. All RPR titers were determined simultaneously at a central laboratory. Results Four hundred and seventy patients had data available for at least 2 of 3 RPR measurements. Overall, 20% of patients showed a titer increase of at least 1 dilution in the 14 days after therapy. The greatest proportion of titer increases following therapy was observed in patients with primary syphilis. Comparing outcome of therapy using the initial (day 0) RPR titer versus the maximal RPR titer (during 14 days) resulted in outcome reclassification in 2.98% of participants. Conclusions Despite the fact that about 20% of early syphilis patients had increases in RPR titers immediately after treatment, these changes rarely influenced assessment of therapeutic outcome. Only 3% of patients treated would have been reclassified.

In a randomized trial among African women with recurrent genital herpes, episodic acyclovir therapy resulted in modestly greater likelihood of lesion healing (HR=1.48, p=0.098; mean 5.1 vs. 6.0 days) and cessation of HSV shedding (HR=1.88, p=0.008; mean 3.0 vs. 5.0 days) compared with placebo, similar to results from high-income countries. (ClinicalTrials.gov registration NCT00808405).

Background While pre-exposure prophylaxis (PrEP) is a promising strategy for reducing HIV transmission, persons at highest risk for infection are not being adequately reached, particularly Black Men who have Sex with Men (MSM). Methods In December 2015, a dedicated PrEP clinic was established at Duke University Medical Center in Durham, North Carolina (NC). We performed a retrospective review of patients evaluated at the PrEP clinic, abstracting the following routinely collected variables: age, race, ethnicity, sex at birth, self-identified gender, HIV risk factors and source of referral. Descriptive statistics are presented as medians and frequencies. Results Over 18 months, 91 patients were evaluated. Most were male (90%, n = 82), approximately half were non-Hispanic Black (46%, n = 42), and median age was 31 years (range 19–66). Most patients identified as MSM (78%, n = 71) and 3 (3%) were transgender women who have sex with men (TGW). Specifically, 30% (n = 27) were Black MSM or TGW. Risk factors for all patients included multiple sexual partners (65%), known HIV+ partner (19%), or a recent sexually transmitted infection (16%). One-quarter of patients (n = 23) were uninsured. Among all Black patients, the most common source of referral was a community-based organization (CBO) (40%, n = 17), and specifically, Black MSM and TGW were most commonly referred by a CBO (44%, n = 12). Among White patients, most were self-referrals (47%, n = 18). Demographic characteristics of our patient population relative to those newly diagnosed with HIV in NC in 2015 are shown in Table 1. Conclusion Although further efforts are needed to improve PrEP uptake in underserved populations in NC, the racial breakdown of our PrEP clinic is more representative of the national HIV epidemic as compared with all PrEP users in the US. Our study demonstrates that community partnerships can be a valuable avenue for patient recruitment and achieve success in reaching Black MSM with messages about PrEP. Disclosures All authors: No reported disclosures.

Trichomonas vaginalis (TV) is a common sexually transmitted infection that can cause vaginitis, cervicitis and urethritis. Persistent and recurrent TV infections are frequent in women, potentially due to the lack of routine screening recommendations for this pathogen, the chronic nature of some infections, and drug resistance. Metronidazole and tinidazole are two oral drugs that are effective against trichomoniasis. There are few alternative treatment options for persons with a metronidazole allergy or treatment failure. Most TV isolates from women with treatment failures that have been analyzed for susceptibility testing in the United States have exhibited low-level metronidazole resistance, supporting the initial use of tinidazole for patients who fail metronidazole therapy. Several non-nitroimidazole drugs and other agents have demonstrated acceptable in vitro activity or cure rates in case reports for metronidazole-resistant trichomoniasis; however, clinical trials are imperative to evaluate their efficacy as alternative therapeutic regimens for this highly prevalent infection.

Recent advances in tests for the sexually transmitted protozoan parasite Trichomonas vaginalis have increased opportunities for diagnosis and treatment of this important sexually transmitted infection. This review summarises currently available tests, highlighting their performance characteristics, advantages and limitations. The recent development of molecular tests for the detection of T vaginalis, including rapid antigen detection and nucleic acid amplification tests, has significantly improved the quality of diagnostics for trichomoniasis, particularly in women. In light of the expanded menu of testing options now available, improved recognition and better control of trichomoniasis are in sight, which should enable the eventual reduction of adverse reproductive consequences associated with T vaginalis infection.

Background Durham County, North Carolina, faces high rates of human immunodeficiency virus (HIV) infection (with or without progression to AIDS) and sexually transmitted diseases (STDs). We explored the use of health care services and the prevalence of coinfections, among HIV-infected residents, and we recorded community perspectives on HIV-related issues. Methods We evaluated data on diagnostic codes, outpatient visits, and hospitalizations for individuals with HIV infection, STDs, and/or hepatitis B or C who visited Duke University Hospital System (DUHS). Viral loads for HIV-infected patients receiving care were estimated for 2009. We conducted geospatial mapping to determine disease trends and used focus groups and key informant interviews to identify barriers and solutions to improving testing and care. Results We identified substantial increases in HIV/STDs in the southern regions of the county. During the 5-year period, 1,291 adults with HIV infection, 4,245 with STDs, and 2,182 with hepatitis B or C were evaluated at DUHS. Among HIV-infected persons, 13.9% and 21.8% were coinfected with an STD or hepatitis B or C, respectively. In 2009, 65.7% of HIV-infected persons receiving care had undetectable viral loads. Barriers to testing included stigma, fear, and denial of risk, while treatment barriers included costs, transportation, and low medical literacy. Limitations Data for health care utilization and HIV load were available from different periods. Focus groups were conducted among a convenience sample, but they represented a diverse population. Conclusions Durham County has experienced an increase in the number of HIV-infected persons in the county, and coinfections with STDs and hepatitis B or C are common. Multiple barriers to testing/treatment exist in the community. Coordinated care models are needed to improve access to HIV care and to reduce testing and treatment barriers.

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.

SETTING Pulmonary tuberculosis (TB) patients reported in North Carolina (NC), USA, from 1996 to 2008 (inclusive). OBJECTIVE To compare prevalence of cavitary TB as a surrogate marker for advanced disease in low-caseload counties with high-caseload counties. DESIGN A multivariate log binomial regression model was used to estimate prevalence ratios (PRs) for cavitary TB. RESULTS The proportion of TB cases in low-caseload counties vs. the total number of TB cases in NC over the study period increased from 10% in 1996 to 20% in 2008. After adjusting for human immunodeficiency virus (HIV) status, excess alcohol use and report year, patients in rural areas of low-caseload counties had greater prevalence (PR 1.40, 95%CI 1.19-1.64) of cavitary disease compared with patients from rural areas of high-caseload counties. The prevalence of cavitary TB did not differ between urban residents of high- or low-caseload counties (PR 1.00, 95%CI 0.86-1.16) after adjusting for HIV status, excess alcohol use and report year. DISCUSSION TB patients in rural areas of low-caseload counties presented with more advanced TB disease compared with patients from urban and/or high-caseload counties. Barriers to timely recognition of TB in rural low-caseload settings must be considered in TB control programs.

Trichomonas vaginalis (TV) infection is the most prevalent curable sexually transmitted infection in the United States and worldwide. Most TV infections are asymptomatic, and the accurate diagnosis of this infection has been limited by lack of sufficiently sensitive and specific diagnostic tests, particularly for men. To provide updates for the 2010 Centers for Disease Control and Prevention’s Sexually Transmitted Diseases Treatment Guidelines, a PubMed search was conducted of all TV literature published from 9 January 2004 through 24 September 2008. Approximately 175 pertinent abstracts and articles were reviewed and discussed with national experts. This article describes advances in TV diagnostics which have led to an improved understanding of the epidemiology of this pathogen, as well as potential biologic and epidemiological interactions between TV and human immunodeficiency virus (HIV). New data on treatment outcomes, metronidazole-resistant TV, management of nitroimidazole-allergic patients, frequency of recurrent TV infection following treatment, and screening considerations for TV in certain populations are also presented.

Background Syphilis remains an important source of morbidity worldwide. Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world. Because of hesitation to use penicillin for fear of anaphylaxis, there is a need for an effective, well-tolerated alternative to penicillin for syphilis therapy. Methods This multicenter, randomized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases. We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly. Results A total of 517 participants were enrolled in the trial. In the intention-to-treat analysis, after 6 months of follow-up, serological cure was observed in 180 (77.6%) of 232 azithromycin recipients and 186 (78.5%) of 237 penicillin recipients (1-sided lower bound 95% confidence interval, 7.2%). Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients (61.5% vs 46.3%), and such adverse events were accounted for, in large part, by self-limited gastrointestinal complaints. Conclusions In this trial, the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection.

Latino immigrants in the United States are disproportionally impacted by the HIV epidemic but face barriers to clinic-based testing. We assessed a community-based strategy for rapid HIV testing by conducting “door-to-door” outreaches in apartments with predominately Latino immigrants in Durham, North Carolina, that has experienced an exponential growth in its Latino population. Eligible persons were 18 years or older, not pregnant, and reported no HIV test in the previous month. Participants were asked to complete a survey and offered rapid HIV testing. Of the 228 Latino participants, 75.4% consented to HIV testing. There was a high prevalence of sexual risk behaviors among participants, with 42.5% acknowledging ever having sex with a commercial sex worker (CSW). Most (66.5%) had no history of prior HIV testing. In bivariate analysis, perceived HIV risk, no history of HIV testing, sex with a CSW, sex in exchange for drugs or money, living with a partner, and alcohol use were significantly associated with test acceptance. In the multivariate analysis, participants who had never been tested for HIV were more likely to consent to rapid HIV testing than those who had tested in the past (adjusted odds ratio 2.5; 95% confidence interval [CI], 1.1, 5.6). Most participants supported rapid HIV testing in the community (97%). Door-to-door rapid HIV testing is a feasible and acceptable strategy for screening high-risk Latino immigrants in the community. Factors associated with HIV risk among Latino migrants and immigrants in the United States should be considered along with novel testing strategies in HIV prevention programs.

Kingella kingae can cause invasive pediatric infections and outbreaks of osteomyelitis/septic arthritis in daycare facilities have been described. This is the first reported public health investigation prompted by a case of K. kingae endocarditis in an infant attending a daycare facility. A concurrent case of osteomyelitis was identified. Screening of daycare contacts revealed a low rate of colonization before antibiotic prophylaxis.

BACKGROUND:: Hormonal contraception use by women may increase the risk of acquiring certain sexually transmitted infections. We explored the effect of hormonal contraceptive use specifically oral contraception (OC) and depot-medroxyprogesterone acetate (DMPA) on Trichomonas vaginalis infections in women. METHODS:: We examined data from a prospective case-control study of women with trichomoniasis and noninfected female patients recruited from 3 public sexually transmitted disease clinics. Women with positive wet mount microscopy or T. vaginalis culture results were classified as having trichomoniasis. Participants underwent physical examinations sexually transmitted infections testing and completed questionnaires which included information about demographics sexual behavior douching and contraceptive use. We assessed the association between hormonal contraceptives and trichomoniasis using bivariable and multivariable analysis and estimated exposure odds ratios (ORs) and adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS:: We identified 427 women with trichomoniasis and 144 uninfected women who had information reported about contraception use. Compared with nonhormonal contraceptive use OC use was negatively associated with trichomoniasis in bivariable analysis (OR: 0.5; 95% CI: 0.3-0.8). This association was no longer statistically significant after adjusting for demographic variables douching and condom use (aOR: 0.9; 95% CI: 0.5-1.6). Use of DMPA compared with nonhormonal contraceptive use was not associated with trichomoniasis in bivariable or multivariable analyses (OR: 1.0 95% CI: 0.5-2.1; aOR = 1.4 95% CI: 0.6-3.4 respectively). CONCLUSIONS:: Although OC use appeared to have a protective effect in the bivariable analysis the hormonal contraceptives OC and DMPA were not associated with T. vaginalis infection after adjustment for other factors.

An epidemic of HIV infections among college students who are primarily men who have sex with men (MSM) have been reported from North Carolina, a state with one of the highest syphilis rates in the southeastern United States. We assessed the proportion of early syphilis coinfections among young HIV-infected individuals statewide and associated risk factors. From January 2002 to July 2006, chart abstractions were performed from North Carolina surveillance records for newly diagnosed HIV-positive men 18-30 years of age reported between 2000-2005, and a subset of women in the same age group. Bivariable and multivariable analyses were conducted to assess early syphilis risk factors among HIV-infected persons. During the 6-year period, there were 1460 HIV-positive men aged 18-30 years reported in North Carolina; 90 (6.2%) were coinfected with early syphilis without a significant change over time. Data were available for 551 HIV-positive women diagnosed from 2002-2005; only 6 (1.1%) were coinfected. Fifty-five percent of coinfected men were diagnosed with both infections on the same date of evaluation. Young HIV-infected men who are black (adjusted odds ratio [aOR] 2.3; 95% confidence interval [CI], 1.3, 4.1), MSM (aOR 3.8; 95% CI, 1.8, 7.8), or reported sex with both genders (aOR 5.1; 95% CI, 2.2, 11.5), or anonymous sex (aOR 2.1; 95% CI, 1.3, 3.3) were more likely to have early syphilis. Although male coinfections have not increased over time, early syphilis has become endemic among young HIV-positive men statewide, emphasizing the need to provide screening for both infections among high-risk individuals.

The effect that vaginal lactobacilli have on trichomoniasis is not known. At 3 clinics for treatment of sexually transmitted disease, we recruited 521 female patients with trichomoniasis and 176 control subjects. All participants underwent physical examinations and testing for sexually transmitted infection and completed questionnaires. Low levels of vaginal lactobacilli were associated with trichomoniasis (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.4-3.2]). After adjustment for covariables, this association remained in women with a higher educational level (OR, 4.6 [95% CI, 2.2-9.5]) but not in women with a lower educational level (OR, 1.6 [95% CI, 0.7-3.4]). Vaginal lactobacilli may be associated with trichomoniasis in women with higher levels of education or a related behavioral factor.

Patients from five clinics in North and South Carolina who had lesions suggestive of primary or secondary syphilis were evaluated using molecular techniques that allow the differentiation of Treponema pallidum strains on the basis of two variable genes, tpr and arp . Lesion samples were screened for the presence of T. pallidum DNA using PCR for polA , which represents a segment of the polymerase I gene that is unique to the spirochete. Twenty-seven of 154 lesion samples were found to contain T. pallidum , 23 of which had typeable DNA. Seven molecular subtypes were found (10f, 12f, 13f, 14f, 14g, 15f, and 16f); one to four subtypes were identified at each clinic. Subtype 14f was found in 52% of the typeable specimens and was distributed in four of the five clinics. Subtype 16f was found in 22% of specimens and was concentrated at one clinic. Further data are needed to define the role of this technique in examining the epidemiology of syphilis.

Objectives: A survey was conducted to ascertain the adherence of health care providers (HCPs) to national guidelines recommending human immunodeficiency virus (HIV) testing among persons with sexually transmitted diseases (STDs) and STD testing among HIV-infected persons. Study: A random sample of HCPs reporting STD and HIV cases in New Jersey were surveyed regarding their STD/HIV testing and reporting practices. Results: Questionnaires were returned by 90 of 162 (55.5%) STD and 73 of 135 (54.1%) HIV HCPs. Sixty-six percent of STD HCPs reported offering HIV testing to persons with gonorrhea, chlamydia, or syphilis. However, up to 42.1% of HIV HCPs who managed HIV-positive patients never or almost never performed initial STD screening in these patients. Among HIV-infected patients, 36.4% of HIV HCPs reported that they never or almost never conducted annual gonorrhea or chlamydia screening in women; 48.6% never conducted screening in men. Conclusions: Further efforts are needed to optimize the implementation of national guidelines for STD/HIV coinfection testing.

Trichomonas vaginalis infection is highly prevalent worldwide and is associated with poor birth outcomes and enhanced human immunodeficiency virus transmission. Traditional detection methods rely on microscopic examination of vaginal specimens (wet mount) and culture, which can be insensitive and time-consuming. More than 3,000 women attending two sexually transmitted disease clinics were enrolled in this cross-sectional study to evaluate urine-based PCR for detection of T. vaginalis using a combined reference standard of wet mount and culture from vaginal swab. The prevalence of trichomoniasis in the population was 16.7% (502 of 3,009 women) using the reference standard. PCR with urine combined with agarose gel-based detection was 66.9% sensitive and 98.3% specific compared to the reference standard. Detection of PCR products using an unlabeled enzyme-linked immunosorbent assay (ELISA) improved the sensitivity to 86.4%, but specificity fell to 86.1%. Using a digoxigenin-labeled ELISA for detection of amplified T. vaginalis DNA from urine, the sensitivity and specificity of the PCR improved to 90.8 and 93.4%, respectively, compared to wet mount or culture from vaginal swabs. For clinical research settings in which vaginal specimens are not available and culture conditions are not feasible, urine-based PCR-ELISA may be useful for the detection of trichomoniasis in women.

High rates of sexually transmitted diseases (STDs) have been reported in military populations. However, it remains uncertain whether the incidence of STDs is higher among military personnel than in the civilian population. The annual incidence of gonorrhea and chlamydia from 1985 through 1996 at Fort Bragg, North Carolina, was determined by use of a clinic database and demographic information for the entire installation. A direct standardization for age, sex, and race/ethnicity was performed, and the adjusted annual rates among active duty soldiers were compared with rates among men and women in North Carolina and the United States. Results showed that the adjusted incidence of gonorrhea and chlamydia among Fort Bragg soldiers remained higher overall than comparable state and national rates during the period of analyses. The 1996 adjusted chlamydia rates for male and female active duty soldiers were 3-fold to 6-fold higher than rates for males and females in North Carolina and in the United States as a whole. STDs continue to lead to significant morbidity in this representative military population.

Transmission through sexual contact accounts for 75 to 85 percent of the nearly 28 million infections with the human immunodeficiency virus (HIV) that have occurred so far.1 The probability of infection through sexual contact, although it varies greatly, appears to be lower than that of infection through other routes of exposure (Figure 1). The variability observed among and within routes of HIV exposure depends partly on the viral dose and also on whether the virus is transmitted directly into the blood or onto a mucous membrane. In addition, these differences are influenced by a variety of host factors, including both . . .

Objective To investigate the role of the opioid system in the pathophysiology of silent ischemia through opiate antagonism with naloxone, and to determine the reproducibility of resting and postexercise beta-endorphin levels in predominantly asymptomatic patients with coronary artery disease. Design Randomized, double-blind, placebo-controlled crossover trial. Setting A University hospital referral center. Patients Ten patients with prior evidence of silent exercise-induced ischemia were studied. Intervention An infusion of saline placebo or naloxone at two dose regimens of 0.015 mg/kg or 0.15 mg/kg before supine exercise testing during three separate occasions for each patient. Outcome measures Plasma beta-endorphin was measured at rest, immediately after exercise, and 5 min poststress. Timing and severity of angina and exercise hemodynamics were also determined. Results Seven of 10 patients reported no angina, whereas the other three experienced angina with placebo and after administration of naloxone at both doses. The severity and duration of angina was consistently noted to decrease in these patients after naloxone administration, especially after low-dose naloxone relative to placebo. There were no apparent correlations between beta-endorphin levels and the characteristics of angina in these three patients, nor between beta-endorphin and hemodynamic responses in all patients in the study. Conclusions (a) naloxone failed to precipitate angina in this population of patients with silent ischemia; (b) naloxone appears to exert an analgesic effect at low doses; and (c) a variability of 5 pM at rest and 13 pM after exercise might be expected in predominantly asymptomatic patients due to random variation, which is comparable with results found in normal subjects.