Clinical Diagnosis Is Highly Predictive of Laboratory-Confirmed Mpox in a Sexual Health Clinic.

BACKGROUND: Promptly recognizing mpox can facilitate earlier diagnosis and appropriate treatment. How accurately clinicians can diagnose mpox based on clinical data and before receiving molecular test results is not known. METHODS: Leveraging public health and clinical data collected in Seattle-King County's Sexual Health Clinic (SHC) from July 29, 2022, to September 30, 2022, we analyzed the proportion of patients who received presumptive versus results-based tecovirimat when clinicians had a high, intermediate, or low suspicion for mpox after clinical evaluation. We calculated the sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) of this approach against criterion standard mpox polymerase chain reaction (PCR) results. RESULTS: Of 321 patients evaluated for mpox in the SHC, median age was 34.5 years and 88% were cisgender men. Overall, 121 of 319 (38%) tested positive by mpox PCR. Clinicians had high suspicion for mpox in 122 patients and offered empiric tecovirimat to 92 (88%), of whom 85 (92%) tested PCR positive. Of 13 intermediate suspicion patients offered presumptive therapy, all accepted but none tested positive by PCR. The sensitivity, specificity, PPV, and NPV of high/intermediate clinical suspicion for mpox were 99%, 90%, 86%, and 99%, respectively. A higher proportion of people with HIV were diagnosed with mpox (57% vs. 36%, P = 0.01, χ2 test), and sensitivity and PPV of high/intermediate clinical suspicion in this subgroup were 100% and 86%, respectively. CONCLUSIONS: Clinical providers working in a high-volume, public SHC were able to both accurately identify and rule out mpox based on clinical examination before receiving PCR test results.

The National Sexually Transmitted Disease Curriculum Podcast as a Method to Increase Sexually Transmitted Infection Education for Health Care Professionals.

BACKGROUND: Podcasts are a valuable educational tool that are convenient and provide on-demand learning. We launched the National Sexually Transmitted Disease Curriculum (NSTDC) Podcast in 2020 to educate health care professionals on sexually transmitted infections with an emphasis on content from peer-reviewed literature relevant to clinical practice. METHODS: We describe the reach and usage data for 31 podcast episodes produced during the first 29 months. Information was obtained via Google Analytics, Apple Podcasts, the podcast hosting platform Buzzsprout, and the Health Professional Application for Training form for listeners who were registered on the NSTDC website. RESULTS: There were more than 21,000 downloads, with an average of 686 downloads per episode. Although 85% of downloads occurred in the United States, podcast visitors were located in 57 countries. The 3 most reported professions/disciplines were registered nurse (39.0%), advanced practice nurse (22.5%), and physician (11.3%). Forty-eight percent of visitors had a primary programmatic focus of sexually transmitted diseases, 24% HIV/AIDs, and 18% primary care. CONCLUSION: The NSTDC Podcast is a highly utilized resource for mobile and on-demand learning for health care professionals who want to expand their knowledge on sexually transmitted infections.

Impact of Text-Based Monthly Check-Ins on Pre-Exposure Prophylaxis Retention at a Sexual Health Clinic.

ABSTRACT: We conducted a retrospective cohort study of preexposure prophylaxis patients at the municipal Sexual Health Clinic in Seattle-King County, Washington from 2019 to 2021 to determine whether monthly check-in text messages impacted 4- and 6-month pre-exposure prophylaxis retention. Monthly check-ins did not appear to improve retention above and beyond open-ended texting and appointment reminders.

The Sexual Health Clinic Role in Vaccine and Treatment Access During the 2022 Mpox Outbreak in King County, Washington.

BACKGROUND: Sexual health clinics were frontline providers in the 2022 US mpox public health response, though data on clinic-based mpox vaccine scale-up, diagnoses, and treatment are limited. We describe the role of a public health sexual health clinic (SHC) in King County's mpox response, between 5/23/22-10/31/22. METHODS: In July 2022, the SHC implemented a dedicated vaccine clinic and presumptive tecovirimat treatment (prior to laboratory confirmation) with on-site dispensation. We describe SHC's vaccine scale-up and contribution to clinical care by calculating the weekly number of vaccines administered by SHC and the total number of patients diagnosed and treated for mpox within SHC, and comparing to countywide data. We calculated time from symptom onset to testing and time from testing to treatment, and assessed temporal changes in these metrics using linear regression. RESULTS: The SHC provided ≥1 vaccine doses to 7,442 individuals (10,295 doses), administering 42% of the 24,409 vaccine doses provided countywide, with the greatest contribution in the first week of August (n = 1,562, 58% of countywide vaccinations that week). Of 598 patients evaluated for mpox and tested, 178 (30%) tested positive (37% of countywide cases), and 152 (85% of SHC patients with mpox) received tecovirimat (46% of treatment countywide). Median time from symptom onset to testing decreased from 12 to 6 days (p = 0.045); time from testing to treatment decreased from 4.5 days to 0 days (p < 0.001). CONCLUSION: The SHC was central to mpox vaccination and treatment scale-up, particularly in the first months of the 2022 epidemic.

Asymptomatic and Subclinical Mpox: An Association With Modified Vaccinia Ankara Vaccine.

BACKGROUND: How often mpox causes asymptomatic infections, particularly among persons who have received the Modified Vaccinia Ankara (MVA) vaccine, is unknown. METHODS: We performed mpox polymerase chain reaction testing on rectal and pharyngeal specimens collected from symptomatic and asymptomatic patients at a sexual health clinic in Seattle, WA, between May 2022 and May 2023. Analyses evaluated the prevalence of asymptomatic or subclinical infection and, among persons with polymerase chain reaction-positive tests, the association of MVA vaccination status with the symptomatic infection. RESULTS: The study population included 1663 persons tested for mpox during 2353 clinic visits. Ninety-three percent of study participants were cisgender men and 96% were men who have sex with men. A total of 198 symptomatic patients (30%) had a first mpox-positive test during 664 visits. Eighteen patients (1.1%) tested during 1689 visits had asymptomatic or subclinical mpox based on a positive rectal or pharyngeal test done in the absence of testing done because of clinical suspicion for mpox. Fourteen (78%) of 18 persons with asymptomatic/subclinical mpox and 53 (26%) of 198 persons with symptomatic mpox had received at least 1 dose of the MVA vaccine ( P < 0.0001). Controlling for calendar month, study subjects who received 1 and 2 doses of MVA vaccine were 4.4 (95% confidence interval, 1.3-15) and 11.9 (3.6-40) times more likely to have asymptomatic versus symptomatic mpox, respectively, than persons who were unvaccinated. CONCLUSIONS: Asymptomatic mpox is uncommon. Modified Vaccinia Ankara vaccination is associated with an asymptomatic/subclinical infection among persons with mpox.

Trans-inclusive Sexual Health Questionnaire to Improve Human Immunodeficiency Virus/Sexually Transmitted Infection (STI) Care for Transgender Patients: Anatomic Site-Specific STI Prevalence and Screening.

BACKGROUND: In 2018, the municipal Sexual Health Clinic in Seattle, implemented trans-inclusive questions about sexual behavior, anatomy, gender-affirming surgeries, and sexually transmitted infection (STI) symptoms in the clinic's computer-assisted self-interview (CASI) to improve care for transgender and nonbinary (TNB) patients. METHODS: We calculated test positivity, the proportion of TNB patient visits that received testing for human immunodeficiency virus (HIV); syphilis; pharyngeal, rectal, and urogenital gonorrhea (GC); and chlamydia (CT) before (5/2016-12/2018) and after (12/2018-2/2020) implementation of new CASI questions, and the proportion of asymptomatic patients who received anatomic site-specific screening based on reported exposures. RESULTS: There were 434 TNB patients with 489 and 337 clinic visits during each period, respectively. Nonbinary patients assigned male at birth (AMAB) had the highest prevalence of GC (10% pharyngeal, 14% rectal, 12% urogenital). Transgender women, transgender men, and nonbinary people AMAB had a high prevalence of rectal CT (10%, 9%, and 13%, respectively) and syphilis (9%, 5%, and 8%). Asymptomatic transgender women, transgender men, and nonbinary patients AMAB were more likely to receive extragenital GC/CT screening compared with nonbinary patients assigned female at birth. After implementation of trans-inclusive questions, there was a 33% increase in the number of annual TNB patient visits but no statistically significant increase in HIV/STI testing among TNB patients. CONCLUSIONS: TNB people had a high prevalence of extragenital STIs and syphilis. Implementation of trans-inclusive medical history questions at a clinic that serves cisgender and transgender patients was feasible and important for improving the quality of affirming and inclusive sexual healthcare.

Implementation of Low-Barrier Human Immunodeficiency Virus Care: Lessons Learned From the Max Clinic in Seattle.

Low-barrier care (LBC) for people with human immunodeficiency virus (HIV) is a differentiated service delivery strategy to engage people in HIV treatment who are not well-engaged in conventionally organized HIV medical care. The LBC approach is flexible, but experience suggests that the intervention has distinct core components. This review summarizes our experience implementing one model of LBC, the Max Clinic in Seattle; describes the core components of the intervention; and presents a framework for implementing low-barrier HIV care with the goal of providing a practical guide for clinical and public health leaders seeking to implement a new LBC program. A systematic approach to addressing key factors during LBC implementation can support practitioners to design an LBC approach that fits the local context while maintaining essential elements of the intervention.

Substance Use and Mental Health Comorbidities and Receipt of Specialty Care Among Patients Enrolled in a Low-Barrier HIV Clinic.

Low-barrier care is one model of a differentiated service delivery approach for people with HIV (PWH) who are not engaged in conventionally-organized HIV care. Although psychiatric and substance use disorders are common among patients in low-barrier clinics, approaches to behavioral health service delivery within this context have not been well-described. We conducted a descriptive analysis using retrospective review of medical records to evaluate substance use and psychiatric comorbidities and receipt of behavioral health services among patients in the Max Clinic in Seattle, Washington. Among 227 patients enrolled from 2015 to mid-2020, most had a history of hazardous substance use (85%), a psychiatric diagnosis (69%) or unstable housing (69%) documented in the medical record. Less than half of patients referred for depression treatment (33%) or for opioid use disorder treatment (40%) completed even one specialty care visit. More effective approaches are needed to engage patients in behavioral health services within the context of low-barrier HIV care.

Etiologies of Proctitis at a Sexual Health Clinic in Seattle, Washington From 2011 to 2021.

ABSTRACT: We analyzed microbiologic etiologies of proctitis among patients seen in an urban sexual health clinic during 2011 to 2021. Among 759 cases, 179 (24%) tested positive for Neisseria gonorrhoeae , 171 (23%) for Chlamydia trachomatis , 21 (3%) for herpes simplex virus, 30 (4%) for syphilis, and 73 (10%) for multiple pathogens; no pathogen was identified in 425 (56%).

Feasibility of a novel self-collection method for blood samples and its acceptability for future home-based PrEP monitoring.

BACKGROUND: Most non-clinic based HIV pre-exposure prophylaxis (PrEP) programs require fingersticks to self-collect blood specimens for laboratory monitoring, a technique that often results in inadequate blood volume for quantitative syphilis and HIV serological testing. We evaluated the acceptability and feasibility of using the Tasso OnDemand™ device as a self-sampling method for PrEP monitoring tests and compared results from samples obtained using the Tasso device to clinician-collected blood samples. METHODS: We enrolled study subjects online and in a sexual health clinic and HIV clinic in Seattle, WA, USA to assess the acceptability of blood self-sampling and preferences for home-based PrEP monitoring. We compared HIV antigen/antibody, quantitative rapid plasma reagin and creatinine results in paired self-collected and clinical specimens collected from a subset of participants. RESULTS: Of 141 participants, 124 (88%) were interested in collecting samples for PrEP monitoring at home. Among 48 who completed blood collections, 94% found the Tasso device easy to use and 95% felt they could perform self-sampling at home. Of 27 participants who used two devices, 100% collected sufficient blood to perform up to two tests while 33% collected sufficient serum for three tests. Agreement in test results between paired samples was high. CONCLUSIONS: These pilot data suggest that using the Tasso self-collection device is acceptable and could feasibly be used to obtain serum specimens sufficient for guideline-recommended PrEP monitoring, though use of a larger volume device may be preferable.

The need for sexual health clinics, their future role, and contribution to public health.

Specialised sexual health clinics (SHCs) play an important role in addressing the staggering rates of STIs seen in many high-income nations. Despite increasing healthcare coverage in the US and nationalised health care in some countries, there is a continued need for SHCs to meet the needs of patients and the community, especially for high-priority populations: those at high risk of STI acquisition and/or groups historically marginalised and underserved in the traditional healthcare system. We need to mobilise resources to support a stronger clinical infrastructure in specialised SHCs. This review describes the importance of SHCs, their future role, and some of the innovative programs housed within SHCs in the US, Australia, and the Netherlands to address both STI and HIV prevention for the populations they serve.

Otosyphilis: A Review of the Literature.

The number of cases of syphilis has increased in the United States and in many high-income nations. Otosyphilis is a less recognized complication of syphilis that can lead to irreversible sensorineural hearing loss. Different pathophysiological mechanisms have been proposed to explain hearing loss in otosyphilis. We review the literature on otosyphilis in adults and propose the need for future work in this field to identify better ways to diagnose, treat, and manage this disease. Patients with syphilis should be screened routinely for hearing loss, and all patients with new, sudden, or fluctuating sensorineural hearing loss should be evaluated for syphilis.

Evaluation of an Emergency Department and Hospital-Based Data Exchange to Improve HIV Care Engagement and Viral Suppression.

BACKGROUND: Emergency department (ED) visits and inpatient (IP) admissions may provide an opportunity to reengage poorly engaged people living with HIV and facilitate viral suppression. In 2015, Public Health Seattle and King County partnered with the University of Washington Medicine to implement a real-time data exchange to identify virally unsuppressed people living with HIV seen at the ED/IP hospital and reengage them in HIV care. We evaluated the impact of the data exchange on care engagement and viral suppression. METHODS: Public Health Seattle and King County received a text alert on weekdays 8 AM to 6 PM for ED/IP patients previously diagnosed with HIV with a most recent viral load ≥200 copies/mL. We compared viral load testing <3 months and viral suppression <6 months after an alert-eligible visit in the 2 years after intervention and the 7 to 30 months before intervention. To account for secular trends, we used difference-in-differences models to compare patients with alert-window visits to patients with visits outside the alert window before and after intervention. RESULTS: Patients with visits within the alert window in the postintervention period were 1.08 (95% confidence interval [CI], 0.97-1.20) times more likely to have a viral load test within 3 months after an ED visit/IP admission and 1.50 (95% CI, 1.27-1.76) times more likely to achieve viral suppression within 6 months than patients in the preintervention period. However, care engagement (difference-in-differences relative risk, 1.00; 95% CI, 0.84-1.18) and viral suppression (difference-in-differences relative risk, 1.01; 95% CI, 0.84-1.20) trends were similar among patients with visits outside the alert window. CONCLUSIONS: Real-time data exchange with ED/IP hospitals was associated with improved viral suppression, but not increased care engagement. However, our results may reflect secular trends resulting from diverse interventions, of which ours was only one. More efforts are needed to improve the effectiveness of relinkage interventions guided by real-time data exchange.

Viral Genetics Modulate Orolabial Herpes Simplex Virus Type 1 Shedding in Humans.

BACKGROUND: Orolabial herpes simplex virus type 1 (HSV-1) infection has a wide spectrum of severity in immunocompetent persons. To study the role of viral genotype and host immunity, we characterized oral HSV-1 shedding rates and host cellular response, and genotyped viral strains, in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A total of 29 MZ and 22 DZ HSV-1-seropositive twin pairs were evaluated for oral HSV-1 shedding for 60 days. HSV-1 strains from twins were genotyped as identical or different. CD4+ T-cell responses to HSV-1 proteins were studied. RESULTS: The median per person oral HSV shedding rate was 9% of days that a swab was obtained (mean, 10.2% of days). A positive correlation between shedding rates was observed within all twin pairs, and in the MZ and DZ twins. In twin subsets with sufficient HSV-1 DNA to genotype, 15 had the same strain and 14 had different strains. Viral shedding rates were correlated for those with the same but not different strains. The median number of HSV-1 open reading frames recognized per person was 16. The agreement in the CD4+ T-cell response to specific HSV-1 open reading frames was greater between MZ twins than between unrelated persons (P = .002). CONCLUSION: Viral strain characteristics likely contribute to oral HSV-1 shedding rates.

Confronting Rising STIs in the Era of PrEP and Treatment as Prevention.

PURPOSE OF REVIEW: This study aims to review the epidemiology of sexually transmitted infections (STIs) among men who have sex with men (MSM) and suggest control measures. RECENT FINDINGS: Despite declines in new HIV diagnosis, bacterial STIs among MSM have dramatically risen since the late 1990s. This increase occurred concurrent with introduction of effective antiretroviral therapy, the advent of electronic mechanisms for meeting sex partners and population-level changes in sexual behavior, including decreased condom use. HIV pre-exposure prophylaxis (PrEP) is now further diminishing condom use, though its impact on STIs is uncertain. A plan to confront the MSM STI epidemic should include increased HIV/STI testing promoted through expanded public health clinical infrastructure, health care system reform to improve the care of gender and sexual minorities and promote low-barrier care, re-invigorated condom promotion, and scientific innovation. There is an urgent need to implement new STI control measures while continuing to expand PrEP use.

Prospective cohort study showing persistent HSV-2 shedding in women with genital herpes 2 years after acquisition.

OBJECTIVES: Herpes simplex virus type 2 (HSV-2) is a prevalent infection with great variability in clinical and virological manifestations among individuals. This prospective cohort study aims to evaluate the natural history of HSV-2 reactivation in the genital area in the same group of women over time. METHODS: Eighteen immunocompetent HSV-2 seropositive women were evaluated for viral shedding for 70 consecutive days within a median of 8 months (range 1-24 months) of HSV-2 acquisition and again approximately 2.5 years later from the original study. Participants obtained daily swabs of genital secretions for HSV PCR and recorded genital symptoms. RESULTS: The viral shedding rate was 29% during the initial study and 19% in the follow-up study (32% reduction, P=0.019). Subclinical shedding rate also decreased from 24% to 13% (37% reduction, P=0.032), as did the rate of days with genital lesions from 22% to 15% (33% reduction, P=0.24). The mean copy number during viral shedding remained unchanged over time at 4.8 log10 c/mL (SD=2.0 and 1.6 during each study, respectively, P=0.33). Women with high viral shedding rates in the past were likely to continue to have high shedding rates (r=0.63, P=0.005). CONCLUSIONS: Despite some reduction, high viral shedding rates persist in women with genital HSV-2 greater than 2 years after acquisition.

Extensive CD4 and CD8 T Cell Cross-Reactivity between Alphaherpesviruses.

The Alphaherpesvirinae subfamily includes HSV types 1 and 2 and the sequence-divergent pathogen varicella zoster virus (VZV). T cells, controlled by TCR and HLA molecules that tolerate limited epitope amino acid variation, might cross-react between these microbes. We show that memory PBMC expansion with either HSV or VZV enriches for CD4 T cell lines that recognize the other agent at the whole-virus, protein, and peptide levels, consistent with bidirectional cross-reactivity. HSV-specific CD4 T cells recovered from HSV-seronegative persons can be explained, in part, by such VZV cross-reactivity. HSV-1-reactive CD8 T cells also cross-react with VZV-infected cells, full-length VZV proteins, and VZV peptides, as well as kill VZV-infected dermal fibroblasts. Mono- and cross-reactive CD8 T cells use distinct TCRB CDR3 sequences. Cross-reactivity to VZV is reconstituted by cloning and expressing TCRA/TCRB receptors from T cells that are initially isolated using HSV reagents. Overall, we define 13 novel CD4 and CD8 HSV-VZV cross-reactive epitopes and strongly imply additional cross-reactive peptide sets. Viral proteins can harbor both CD4 and CD8 HSV/VZV cross-reactive epitopes. Quantitative estimates of HSV/VZV cross-reactivity for both CD4 and CD8 T cells vary from 10 to 50%. Based on these findings, we hypothesize that host herpesvirus immune history may influence the pathogenesis and clinical outcome of subsequent infections or vaccinations for related pathogens and that cross-reactive epitopes and TCRs may be useful for multi-alphaherpesvirus vaccine design and adoptive cellular therapy.

Herpes Simplex Virus Type 1 Shedding in Tears and Nasal and Oral Mucosa of Healthy Adults.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) is prevalent worldwide and causes mucocutaneous infections of the oral area. We aimed to define the frequency and anatomic distribution of HSV-1 reactivation in the facial area in persons with a history of oral herpes. METHODS: Eight immunocompetent HSV-1 seropositive adults were evaluated for shedding of HSV-1 from 12 separate orofacial sites (8 from oral mucosa, 2 from nose, and 2 from conjunctiva) 5 days a week and from the oral cavity 7 days a week for approximately 5 consecutive weeks by a HSV DNA PCR assay. Symptoms and lesions were recorded by participants. RESULTS: Herpes simplex virus type 1 was detected at least from 1 site on 77 (26.5%) of 291 days. The most frequent site of shedding was the oral mucosa, with widespread shedding throughout the oral cavity. Lesional shedding rate was 36.4% (4 of 11 days with lesions), and the asymptomatic rate was 27.1% (65 of 240 nonlesional days). In individual participants, the median rate of HSV shedding by HSV PCR was 19.7% of days (range, 11%-63%). CONCLUSIONS: Reactivation of HSV-1 on the oral mucosa is common and usually asymptomatic. However, HSV-1 is rarely found in tears and nasal mucosa. Frequent oral shedding of HSV-1 may increase the risk for transmitting the virus to both oral and genital mucosa of sexual partners.

On The Horizon: Novel Approaches to Sexually Transmitted Infection Prevention.

Rates of sexually transmitted infections (STIs), especially cases of infectious and congenital syphilis, are increasing in the United States. Novel strategies for STI prevention are being explored and include doxycycline post-exposure prophylaxis and the potential utility of vaccines against gonorrhea. Self-collection of samples and point of care testing for STI are increasingly being employed in a variety of settings. Both can improve uptake of screening and lead to earlier detection and treatment of incident STI in target populations. Overcoming existing regulatory issues and optimizing implementation of current evidence-based strategies will be key to maximizing future STI prevention efforts. Here we provide an update for primary care providers on selected new strategies for STI prevention either currently available or under development for possible future use.