Evidence-Informed Provision of Doxycycline Post-Exposure Prophylaxis for Prevention of Bacterial Sexually Transmitted Infections.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces the risk of bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. In the United States, doxy-PEP is in an early stage of integration into clinical practice, and national guidelines for its use were recently released. The goal of this manuscript is to provide practical guidance for clinicians who are considering or currently prescribing doxy-PEP. We address five clinical questions using post hoc analyses of data from the DoxyPEP randomized controlled trial and discuss the potential implications and limitations of each question with the goal of informing clinical practice and implementation of doxy-PEP programs. The questions address patient eligibility criteria for doxy-PEP, the expected benefit and associated doxy-PEP doses for the average patient, the initial number of doses prescribed, and laboratory monitoring of persons taking doxy-PEP.

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.

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.

Using an Innovative Method for Self-Collection of Capillary Blood for HIV and Syphilis Testing Among Men Who Have Sex With Men Who Use Pre-exposure Prophylaxis in the Netherlands; Limburg4zero.

BACKGROUND: Home-based sampling could create accessible testing opportunities for men who have sex with men (MSM) who use pre-exposure prophylaxis (PrEP). Blood collection is required for the most reliable laboratory results for HIV and syphilis testing. An innovative blood collection method (Tasso+) creates a vacuum and semi-automatically collects larger volumes of blood from the upper arm. This study aimed to assess acceptability and feasibility of this device among PrEP-using MSM and the performance of blood collection. METHODS: Between August 2022 and January 2023, 47 MSM were recruited during their routine PrEP consultations at a Dutch Centre for Sexual Health. Participants tested the method directly after consultation, and an online questionnaire determined acceptability and feasibility. Blood and residual serum volumes were measured after sampling and after HIV and syphilis testing. RESULTS: Of the participants, 87% had a positive attitude toward use of the device, and 77% would use it again for self-sampling at home. Participants rated the use of the blood collection device as easy (96%). On average, 536 µL whole blood (244 µL serum) was collected. All samples were tested for HIV and syphilis, and most samples had sufficient blood for routine HIV (91%) and syphilis testing (89%). Most samples (85%) had 220 µL residual blood, sufficient for further testing (e.g., confirmation). CONCLUSIONS: Blood self-sampling with a method that creates a vacuum from the upper arm is highly acceptable by users and performs well in blood collection for multiple tests. This method has promising potential for use in home-based sexual health care for PrEP-using MSM.

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.

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.

Sexually Transmitted Infection Testing Using Online Companies: Benefits, Drawbacks, and Call for Official Guidance.

ABSTRACT: In this brief case series, we outline issues with some online sexually transmitted infection services and delayed reporting of results. Commercial entities providing sexually transmitted infection testing should ensure that all results are reported to local public health jurisdictions and that procedures exist to link persons to appropriate treatment and follow-up.

Association of Arthritis and Antihypertensive Medication Use Among Individuals With Hypertension: A Cross-Sectional Analysis of the 2017 Behavioral Risk Factor Surveillance System.

BACKGROUND: The aim of this study was to assess whether arthritis is associated with lower antihypertensive medication (AHM) use among those with hypertension and whether this relationship differs by age or cardiovascular (CV) comorbidity. METHODS: The data were from the 2017 Behavioral Risk Factor Surveillance System. We employed survey weights to account for the complex sampling design and nonresponse bias. We used generalized linear models to estimate unadjusted and adjusted prevalence ratios (PRs) and 95% confidence intervals comparing AHM use among those with severe or mild arthritis to those without arthritis, stratified by age, sex, and CV comorbidity. RESULTS: Among 173,098 adults with hypertension, 26.0% had severe arthritis and 22.3% had mild arthritis. Compared with those without arthritis, individuals with mild or severe arthritis were older, predominantly female, with lower income and more comorbidities. After adjustment for sex, race, inability to afford medications, and CV comorbidity, the prevalence ratios for AHM use were stronger for younger versus older age groups. Associations did not differ significantly by sex or CV comorbidity. Associations were similar for mild and severe arthritis, compared with no arthritis. CONCLUSIONS: Among individuals with hypertension, those with arthritis had significantly higher prevalences of AHM use compared with those without arthritis. Higher prevalences of AHM use were seen with older age categories, although a stronger association of arthritis and AHM use was found in younger age groups. Future studies on hypertension management in arthritis should examine these relationships more closely.

Hyperammonemia syndrome due to Ureaplasma infection after liver-kidney transplant.

Hyperammonemia syndrome, with high levels of ammonia and neurologic dysfunction, is a syndrome with historically high mortality that may occur after solid organ transplantation. Recently, this has been associated with infection due to Ureaplasma, mostly following lung transplantation. We describe the first case of hyperammonemia syndrome due to Ureaplasma infection after liver-kidney transplantation. Our patient rapidly recovered after specific antibiotic treatment. It is important to consider these infections in the differential diagnosis for encephalopathy post-transplant, as these organisms often do not grow using routine culture methods and polymerase chain reaction testing is typically required for their detection. This is particularly critical after liver transplantation, where a number of other etiologies may be considered as a cause of hyperammonemia syndrome.

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.

Association of Tecovirimat Therapy With Mpox Symptom Improvement: A Cross-sectional Study-King County, Washington, May-October 2022.

Background: Data on tecovirimat effectiveness for human mpox are limited. We conducted a retrospective cross-sectional interview-based study to identify associations between tecovirimat treatment and the mpox clinical course. Methods: Using public health surveillance data from King County, Washington, we recruited and interviewed persons diagnosed with mpox during May-October 2022. We calculated descriptive statistics on demographics, vaccination status, comorbidities, and symptoms including 3 self-reported dates (symptom onset, first date of symptom improvement, and illness resolution). We used multivariable linear regression, stratified by illness severity, to evaluate the association of tecovirimat treatment with time to symptom improvement and time to illness resolution. We compared individuals who did not receive tecovirimat to participants who started tecovirimat early (≤5 days from symptom onset) and late (>5 days and ≤28 days from symptom onset) in their illness. Results: Of 465 individuals diagnosed with mpox, 115 (25%) participated in this study. Eighty participants (70%) received tecovirimat and 43 (37%) initiated tecovirimat early. Sixty-eight (59%) reported severe symptoms during their illness, including proctitis (n = 38 [33%]), rectal bleeding (n = 27 [24%]), or severe pain (n = 24 [21%]). In the multivariable analysis, early tecovirimat was associated with shorter time to symptom improvement (-5.5 days, P = .04) among participants with severe illness but not among those with nonsevere illness (0.9 day, P = .66). Early tecovirimat was not associated with faster illness resolution, regardless of severity. Conclusions: Our small study suggests that early tecovirimat initiation may hasten subjective symptomatic improvement in people with severe mpox. Larger randomized trials are needed to evaluate this finding.

Doxycycline postexposure prophylaxis for prevention of sexually transmitted infections.

Doxycycline postexposure prophylaxis (doxy-PEP) is a novel strategy now demonstrated in several clinical trials to dramatically reduce incidence rates of gonorrhea, chlamydia, and syphilis in some key populations at high risk of sexually transmitted infections. Even so, much remains unknown about the long-term consequences of doxy-PEP, and several concerns, including the potential for the development of antibiotic resistance and disturbances to the microbiome, balance the benefits. This review highlights the history of antibiotic prophylaxis for sexually transmitted infections, and the rationale, current evidence, and future directions for doxy-PEP.

Syphilis: A Modern Resurgence.

Syphilis is an important public health problem in the U.S. and many high-income nations. The rates of syphilis continue to increase and there is an urgent need for medical providers of a variety of backgrounds to recognize this disease. In this review, we cover the key clinical findings of syphilis and provide an overview of the diagnosis and management of this disease in adults.

The Syphilis Epidemic Among Heterosexuals Is Accelerating: Evidence From King County, Washington.

Background: We characterized the rapid increase in syphilis among cisgender women in King County, Washington, and compared it with trends among cisgender men who have sex with men. Method: We used surveillance data from King County, 2007 to 2022, to describe incidence trends stratified by syphilis stage, gender, and gender of sex partners; trends in pregnant cases and congenital syphilis; and trends in rapid plasma reagin titer at diagnosis among late/unknown duration cases. We used joinpoint regression to analyze trends. Results: Among cisgender women, all-stage syphilis incidence remained stable from 2007 to 2010 but then increased by 16.3% per year (95% CI, 12.0%-20.7%) from 2010 to 2020 and 90.1% per year (95% CI, 26.4%-185.9%) from 2020 to 2022. Early syphilis rates rose gradually from 2007 to 2017 (18% per year; 95% CI, 7.4%-29.6%) and then rapidly from 2017 to 2022 (62.5% per year; 95% CI, 24.1%-112.9%). In contrast, the increase in late/unknown duration syphilis incidence was delayed. Among cisgender men who have sex with women, all-stage syphilis remained stable from 2007 to 2014 and increased 25.0% per year (95% CI, 14.0%-37.0%) from 2014 to 2022. Syphilis incidence increased steadily among men who have sex with men, with all-stage incidence increasing 7.0% per year (95% CI, 4.8%-9.2%) from 2007 to 2022. Median rapid plasma reagin titer among late/unknown duration cases increased significantly over the analysis period. Conclusions: An explosive epidemic of syphilis is ongoing in King County. The delayed increase in asymptomatic late/unknown duration cases relative to early symptomatic cases suggests that there is a large and growing reservoir of recently acquired undiagnosed syphilis in women. New clinical and public health activities are urgently needed to control the growing epidemic.

Effectiveness of the Modified Vaccinia Ankara Vaccine Against Mpox in Men Who Have Sex With Men: A Retrospective Cohort Analysis, Seattle, Washington.

Background: Data on modified Vaccinia Ankara (MVA) vaccine effectiveness against mpox in real-world settings are limited. Methods: We performed a retrospective cohort analysis using Cox proportional hazards regression to estimate the association between vaccination and laboratory-confirmed mpox incidence. Study subjects included all men who have sex with men seen in a sexual health clinic in Seattle, Washington, between 1 January 2020 and 31 December 2022. Subjects' receipt of vaccine and diagnosis with mpox were ascertained from public health vaccine registry and surveillance data. Analyses were adjusted for demographic factors, human immunodeficiency virus (HIV) status, and sexual risk behaviors. Results: The incidence of mpox per 100 person-years was 8.83 among patients with 0 doses, 3.32 among patients with 1 dose, and 0.78 among patients with 2 doses of MVA vaccine. Mpox diagnosis was significantly associated with age category 30-39 and 40-51 years, HIV positivity, syphilis diagnosis in the prior year, >10 sex partners in the last year, and having a clinic visit in the last year. In the multivariate model adjusting for these factors, vaccine effectiveness was 81% for 1 dose and 83% for 2 doses. Conclusions: These data support the effectiveness of the MVA vaccine-including a single dose of the vaccine-in preventing mpox disease and highlight the appropriateness of risk factor-based prioritization of immunization early in the epidemic. The durability of MVA vaccine-induced immunity is unknown, and at-risk persons should receive 2 doses of MVA.

Brief Report: Previous Preexposure Prophylaxis Use Among Men Who Have Sex With Men Newly Diagnosed With HIV Infection in King County, WA.

BACKGROUND: Preexposure prophylaxis (PrEP) discontinuations are common and are associated with subsequent HIV acquisition. The population-level impact of PrEP discontinuations is unknown. METHODS: Public health staff routinely asked men who have sex with men (MSM) with newly diagnosed HIV infection about their history of PrEP use as part of partner notification interviews in King County, WA, from 2013 to 2021. We assessed trends in the proportion of MSM who ever took PrEP and described reasons for PrEP discontinuation. RESULTS: A total of 1098 MSM were newly diagnosed with HIV during the study period; of whom, 797 (73%) were interviewed, and 722 responded to questions about their history of PrEP use. Ninety-four (13%) reported ever taking PrEP. The proportion of MSM who ever used PrEP before HIV diagnosis increased from 2.3% in 2014 to 26.6% in 2020-2021 ( P < 0.001 for trend). The median time from PrEP discontinuation to HIV diagnosis was 152 days, and median duration on PrEP was 214 days. Common reasons for stopping PrEP included self-assessment as being at low risk for HIV, side effects, and insurance issues. Nineteen men were on PrEP at the time of HIV diagnosis; mutations conferring emtricitabine/tenofovir resistance were identified in 8 (53%) of 15 men with available genotype data. CONCLUSION: More than 25% of MSM with newly diagnosed HIV from 2020 to 2021 had ever used PrEP. More than 50% who discontinued PrEP were diagnosed <6 months after stopping. Strategies to preempt PrEP discontinuations, enhance retention, and facilitate resumption of PrEP are critical to decrease new HIV diagnoses.

A Demedicalized Model to Provide PrEP in a Sexual Health Clinic.

BACKGROUND: Sexual health clinics (SHCs) serve large numbers of patients who might benefit from preexposure prophylaxis (PrEP). Integrating longitudinal PrEP care into SHCs can overburden clinics. We implemented an SHC PrEP program that task shifted most PrEP operations to nonmedical staff, disease intervention specialists (DIS). METHODS: We conducted a retrospective cohort analysis of PrEP patients in an SHC in Seattle, WA, from 2014 to 2020 to assess the number of patients served and factors associated with PrEP discontinuation. Clinicians provide same-day PrEP prescriptions, whereas DIS coordinate the program, act as navigators, and provide most follow-up care. RESULTS: Between 2014 and 2019, 1387 patients attended an initial PrEP visit, 93% of whom were men who have sex with men. The number of patients initiating PrEP per quarter year increased from 20 to 81. The number of PrEP starts doubled when the clinic shifted from PrEP initiation at scheduled visits to initiation integrated into routine walk-in visits. The percentage of visits performed by DIS increased from 3% in 2014 to 45% in 2019. Median duration on PrEP use was 11 months. PrEP discontinuation was associated with non-Hispanic black race/ethnicity [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.02 to 1.76], age <20 years (HR 2.17, 95% CI: 1.26 to 3.75), age between 20 and 29 years (HR 1.55, 95% CI: 1.06 to 2.28), and methamphetamine use (HR 1.98, 95% CI: 1.57 to 2.49). The clinic had 750 patients on PrEP in the final quarter of 2019. CONCLUSIONS: A demedicalized SHC PrEP model that task shifts most operations to DIS can provide PrEP at scale to high priority populations.

Laboratory Perspective on Racial Disparities in Sexually Transmitted Infections.

BACKGROUND: Rates of sexually transmitted infections (STI) have risen steadily in recent years, and racial and ethnic minorities have borne the disproportionate burden of STI increases in the United States. Historical inequities and social determinants of health are significant contributors to observed disparities and affect access to diagnostic testing for STI. CONTENT: Public health systems rely heavily on laboratory medicine professionals for diagnosis and reporting of STI. Therefore, it is imperative that clinicians and laboratory professionals be familiar with issues underlying disparities in STI incidence and barriers to reliable diagnostic testing. In this mini-review, we will summarize contributors to racial/ethnic disparity in STI, highlight current epidemiologic trends for gonorrhea, chlamydia, and syphilis, discuss policy issues that affect laboratory and public health funding, and identify specific analytic challenges for diagnostic laboratories. SUMMARY: Racial and ethnic disparities in STI in the US are striking and are due to complex interactions of myriad social determinants of health. Budgetary cuts for laboratory and public health services and competition for resources during the COVID-19 pandemic are major challenges. Laboratory professionals must be aware of these underlying issues and work to maximize efforts to ensure equitable access to diagnostic STI testing for all persons, particularly those most disproportionately burdened by STI.