Durham County Department of Public Health

BackgroundDuring the early stages of the coronavirus disease 2019 (COVID-19) pandemic, those with severe COVID-19 infection were at risk for a number of opportunistic infections including COVID-19-associated pulmonary aspergillosis (CAPA). We initiated a randomized clinical trial to evaluate whether isavuconazole, a triazole antifungal, could prevent CAPA and improve survival in patients admitted to the ICU with severe COVID-19 infection. MethodsWe designed a phase III/IV randomized, double-blind, two-arm, placebo-controlled trial evaluating standard of care (SOC) plus isavuconazole versus SOC plus placebo and were to enroll participants admitted to the ICU with severe COVID-19 infection at three medical centers in California, United States. The projected sample size was 162 participants. ResultsDue to poor enrollment and the declining number of COVID-19 cases over time, the study was terminated after 7 participants were enrolled, all enrolled at one study site (UC San Diego Health). CAPA was suspected in two participants and they were started on open-label isavuconazole. One was withdrawn due to possible isavuconazole-related adverse side effects. ConclusionEnrollment was slower-than-expected due to multiple factors, including competing COVID-19-related studies and hesitancy from potential study participants or their families to join the study. Our experience highlights some of the difficulties in planning and running a clinical trial focused on fungal superinfections involving severely ill patients during the height of the COVID-19 pandemic. Lessons learned from this study will help in the design of proposed studies examining antifungal prophylaxis against aspergillosis following other severe respiratory viral infections.

Improvements in diagnostics for invasive mold infections are urgently needed. This work presents a new molecular detection approach that addresses technical and workflow challenges to provide fast pathogen detection, identification, and quantification that could inform treatment to improve patient outcomes.

SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, and their utility and efficacy in antifungal treatment are limited by one or more of innate or acquired resistance in some fungi, poor penetration into "sequestered" sites, and agent-specific side effect which require frequent patient reassessment and monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, and fungicidal mechanism(s) are urgently needed. Here, we provide a comprehensive review of novel antifungal agents, with both improved known mechanisms of actions and new antifungal classes, currently in clinical development for treating invasive yeast, mold (filamentous fungi), Pneumocystis jirovecii infections, and dimorphic fungi (endemic mycoses). We further focus on inhaled antifungals and the role of immunotherapy in tackling fungal infections, and the specific PK/pharmacodynamic profiles, tissue distributions as well as drug-drug interactions of novel antifungals. Finally, we review antifungal resistance mechanisms, the role of use of antifungal pesticides in agriculture as drivers of drug resistance, and detail detection methods for antifungal resistance.

The Centers for Disease Control and Prevention recommends universal retesting within 3months after treatment of Trichomonas vaginalis infection given high rates of persistent infection or reinfection, or if this is not possible, within 12months following treatment. Data is lacking on how often this is actually done. We analyzed the demographic and clinical characteristics, rate of return for the recommended retesting, concordance between wet prep and nucleic acid amplification testing, and percent positivity for T. vaginalis on repeat vaginal specimens at a local public health department in Durham, North Carolina, United States. Of 193 females treated for trichomoniasis between March 1, 2021 - May 31, 2022, 83% were Black or African American and 44% between the ages of 20 and 29years. Of these individuals, 32% had retesting performed within 3 months and 50% within 365days after treatment. Females between the ages of 20 and 29years were more likely to return for retesting than those between the ages of 30 and 39 years. Of those who returned for retesting, 10% were positive on repeat testing. In this study, 50% of females diagnosed with trichomoniasis completed retesting within 365days. Improved scheduling of clients at the time of trichomoniasis treatment and improved identification in our electronic health record of individuals diagnosed with trichomoniasis within the prior year would likely improve retesting rates. Given the high prevalence of trichomoniasis, expanded screening of asymptomatic females in settings where this is feasible may be warranted.

This manuscript focuses on interprofessional education (IPE) using simulation and its use between emergency department and emergency medical services personnel. It explores the theoretical frameworks behind IPE and applies them to simulation-based emergency medical services education. There is a notable lack of research on the use of IPE using simulation between these 2 professions. The need for IPE using simulation as well as barriers and recommendations to remove the barriers are discussed.

Emphysematous osteomyelitis (EO) is a rare condition characterized by the appearance of gas locules within the bone on imaging, usually as a result of anaerobic bacterial infection. We present the case of a 46-year-old known intravenous (IV) drug user who was admitted to the emergency department with intractable pain in the right groin. He was febrile with elevated white cell count and C-reactive protein. He underwent an X-ray and CT of the pelvis which demonstrated intraosseous gas in the proximal right femur. A diagnosis of EO was made radiologically, allowing for prompt antibiotic treatment and a plan for surgical debridement. There are only a handful of published cases of EO in the literature, only one of which has described IV drug use as the underlying factor.

Few studies have examined long-term outcomes among persons who initiate preexposure prophylaxis (PrEP) in the South, including PrEP discontinuation and sexually transmitted infection (STI) rates. Care discontinuation (>6 months without a PrEP appointment) and incident STIs were evaluated for patients at 2 PrEP clinics in Durham, NC. We tested for predictors of discontinuation as a binary variable using logistic regression. Model covariates included age, race/ethnicity, sex, known HIV-positive partner, commercial sex work, men who have sex with men (MSM) versus not MSM, type of insurance, and clinic site. A similar analysis was completed for STI incidence, controlling for days in the study. Among 271 patients, mean age was 33.2 years, 46.9% were Black and 11.1% were Latino, 81.2% were MSM, and 32% were uninsured. Preexposure prophylaxis was discontinued in 47%, and another 11% had intermittent care. Sexually transmitted infection incidence was 45.4/100 person-years, and 5 patients were diagnosed with HIV at baseline or in follow-up. Men who have sex with men were less likely to discontinue PrEP relative to non-MSM (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.10-0.64). Baseline STI was associated with a higher likelihood of incident STI (OR, 8.19; 95% CI, 3.69-19.21), whereas care discontinuation was associated with a lower likelihood of STI (OR, 0.28; 95% CI, 0.11-0.65). Preexposure prophylaxis programs in the Southern United States are reaching uninsured and predominantly Black and Latino MSM, but discontinuation rates are high despite elevated rates of incident STI and HIV. Further work is required to elucidate causes of PrEP discontinuation and encourage persistence in care.

Objectives: Smartphone applications ("apps") can be used to promote health behavior change and expand the reach of behavioral interventions. To date, only a few existing apps have been developed for health promotion among adolescent survivors of childhood cancer. To address this gap, we developed an app-based intervention, using game design characteristics, theory-based behavioral strategies, and assistance from a health coach to motivate health behavior change for adolescent survivors of childhood cancer. This article describes the development and initial feasibility evaluation of the intervention. Methods: Using a theoretical framework and an extensive formative process, we developed an app-based game ("Mila Blooms") that promotes healthy eating and physical activity among adolescent survivors of childhood cancer. A single-arm 8-week intervention, using this app-based game, with assistance from a health coach, was conducted among a sample of pediatric cancer survivors (n = 15) to evaluate its initial feasibility for promoting health behavior change. Results: Results from the feasibility evaluation were encouraging. The majority of enrolled participants were retained throughout the 8-week intervention (93.8%). Participant satisfaction feedback indicated positive experiences, related to ease of use and enjoyment of the app. Although there was little evidence for behavior change attributable to the app in this first stage of development, there was a solid demonstration of the viability and appeal of the game features, and there were no adverse side effects. Conclusions: Results provide insights into how gamification can be used to promote health behaviors through an app-based intervention. Mila Blooms holds promise for promoting health behavior change. Lessons learned from our experiences could be useful for the future development and implementation of app-based adolescent health interventions.