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Infection by Trypanosoma cruzi , the agent of Chagas disease, can irreparably damage the cardiac and gastrointestinal systems during decades of parasite persistence and related inflammation in these tissues. Diagnosis of chronic disease requires confirmation by multiple serological assays due to the imperfect performance of existing clinical tests. Current serology tests utilize antigens discovered over three decades ago with small specimen sets predominantly from South America, and lower test performance has been observed in patients who acquired T. cruzi infection in Central America and Mexico. Here, we attempt to address this gap by evaluating antibody responses against the entire T. cruzi proteome with phage display immunoprecipitation sequencing comprised of 228,127 47-amino acid peptides. We utilized diverse specimen sets from Mexico, Central America and South America, as well as different stages of cardiac disease severity, from 185 cases and 143 controls. We identified over 1,300 antigenic T. cruzi peptides derived from 961 proteins between specimen sets. A total of 67 peptides were reactive in 70% of samples across all regions, and 3 peptide epitopes were enriched in ≥90% of seropositive samples. Of these three, only one antigen, belonging to the trans-sialidase family, has not previously been described as a diagnostic target. Orthogonal validation of this peptide demonstrated increased antibody reactivity for infections originating from Central America. Overall, this study provides proteome-wide identification of seroreactive T. cruzi peptides across a large cohort spanning multiple endemic areas and identified a novel trans-sialidase peptide antigen (TS-2.23) with significant potential for translation into diagnostic serological assays.

Background: Latinx people in the United States are disproportionately diagnosed with HIV and are more likely to experience worse HIV-related health outcomes. Although m-health has demonstrated success in improving HIV care, a gap remains in the development of m-health platforms tailored to Latinx populations. Methods: We conducted formative study to guide the adaptation of an evidence-based m-health intervention, PositiveLinks (PL), for Spanish-speaking Latinx people living with HIV (PLWH). Spanish-speaking Latinx PLWH in the nonurban Southern United States completed semistructured interviews and viewed a demo version of the m-health intervention. Qualitative analysis was performed using a grounded theory approach. Emerging themes were identified in four topic areas: (1) prior experiences with technology, (2) desired m-health features, (3) experiences with prototype app, and (4) iteration of prototype. Results: All PLWH who participated ( n  = 22) were born outside the continental United States. Participants included 10 men, 10 women, and 2 transgender participants. Mean age was 41.1 years (standard deviation 11.6 years). Participants expressed concerns about privacy, a need for reliable information, and interest in practical m-health features such as appointment and medication reminders. After trialing the Spanish-language PL prototype, participants reported that peer support and positive reinforcement were strong motivators to use the app. The ability to individualize the app to meet one's own needs was also considered important. Conclusion: This formative study provides baseline attitudes about m-health among Latinx PLWH as well as desired m-health features. m-Health interventions are acceptable to Spanish-speaking PLWH and involving the target population in a user-centered formative process led to improvements in app accessibility and usability., Competing Interests: K.A.M. reports stock ownership in Gilead Sciences, Inc. R.D. provides consulting services to Warm Health Technology, Inc., which is an entity owned by the UVA Health System Venture Fund that supports dissemination of m-health technology to interested organizations, including the licensed version of PositiveLinks, PLCares. K.A.M., R.D., and J.E.S. have received funding from Gilead Sciences, Inc., for an investigator-initiated trial unrelated to this study. The other authors report no disclosures., (© Tabor E. Flickinger et al., 2021; Published by Mary Ann Liebert, Inc.)

A 42-year-old woman with a history of acute myeloid leukaemia status postallogeneic stem cell transplant presented with fevers, altered mental status, pulmonary infiltrates and septic shock that further progressed to thrombocytopenia and purpura fulminans. Laboratory studies were consistent with a diagnosis of thrombotic thrombocytopenic purpura (TTP). Blood cultures grew Streptococcus pneumoniae On chart review, our patient had a history of low immunoglobulin levels following stem cell transplant, which may have predisposed her to pneumococcal infection. The patient responded to therapy with ceftriaxone, plasma exchange, rituximab and caplacizumab. This is the fourth-documented case of pneumococcal induced TTP and, to the best of our knowledge, the first-describing pneumococcal induced TTP with purpura fulminans. We conclude that patients with TTP should be evaluated for infectious aetiologies and empiric antibiotics should be considered. Clinicians should be aware of the possibility for TTP to lead to purpura fulminans., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Latinx people living with HIV (PLWH) experience disparities in health outcomes and face unique barriers to care related to language, intersectional stigma, and immigration status. We aimed to explore the lived experience of Spanish-speaking Latinx PLWH in the nonurban South to better understand how to improve care for this minority language population. We conducted semistructured interviews with 22 participants (10 men, 10 women, 2 transgender women) who were recruited from a Ryan White HIV/AIDS program (RWHAP) and a community-based organization. Almost all participants were foreign born. Emerging themes included language barriers, cultural differences, inadequate interpreter services, HIV-related and intersectional stigma, isolation, and relationships as a source of support. These barriers may contribute to disparities in outcomes for Latinx PLWH. New interventions are needed to overcome barriers, foster community, and ensure culturally tailored models of care. Potential clinic-level interventions include the development of specialized training for RWHAP interpreters and inclusion of interpreters in care teams.

Coronavirus disease 2019 negatively impacts social determinants of health that contribute to disparities for people with human immunodeficiency virus (HIV). Insecurity of food, housing, and employment increased significantly in April 2020 among patients with lower incomes at a Ryan White HIV/AIDS program clinic in the Southern United States., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Most people diagnosed with hepatitis C virus (HCV) have not linked to care, despite the availability of safe and effective treatment. We aimed to understand why people diagnosed with HCV have not pursued care in the non-urban Southern United States., Methods: We conducted a survey and semi-structured interview with participants referred to an HCV clinic who did not attend an appointment between 2014 and 2018. Our clinic is located in a non-urban region of Virginia at a university hospital. Qualitative data collection was guided by the Health Belief Model (HBM). Data was analyzed using qualitative content analysis to identify key factors influencing patient perceptions regarding HCV and pursuit of care., Results: Over half of previously referred patients (N = 200) could not be reached by phone. Eleven participants enrolled, including 7 men and 4 women. Based on survey responses, unreliable transportation, unstable housing, substance use, and lack of insurance were common. Participants demonstrated good knowledge of HCV disease, complications, and treatment. On qualitative analysis of semi-structured interviews, final themes emerged from within and between HBM constructs. Emerging themes influencing patient perceptions included (1) structural barriers, (2) stigma, (3) prior experiences of HCV disease and treatment, (4) discordance between the recognized severity of HCV and expected impacts on one's own health, and (5) patient-provider relationship. Substance use was not identified to be a barrier to care., Conclusions: Participants perceived individual and structural barriers to linking to care. A strong HCV knowledge base was not sufficient to motivate pursuit of care. Efforts to improve linkage to care must address barriers at multiple levels, and system-level changes are needed. As the majority of previously referred patients could not be contacted by phone, current approaches to patient engagement are not effective for reaching these populations. Expansion of HCV care to primary care settings with an established patient-provider relationship or co-located treatment within substance use treatment programs may serve to increase access to HCV treatment.

Background: Hepatitis C virus (HCV) and the opioid epidemic disproportionately affect the Appalachian region. Geographic and financial barriers prevent access to specialty care. Interventions are needed to address the HCV-opioid syndemic in this region., Methods: We developed an innovative, collaborative telehealth model in Southwest Virginia featuring bidirectional referrals from and to comprehensive harm reduction (CHR) programs and office-based opioid therapy (OBOT), as well as workforce development through local provider training in HCV management. We aimed to (1) describe the implementation process of provider training and (2) assess the effectiveness of the telehealth model by monitoring patient outcomes in the first year., Results: The provider training model moved from a graduated autonomy model with direct specialist supervision to a 1-day workshop with parallel tracks for providers and support staff followed by monthly case conferences. Forty-four providers and support staff attended training. Eight providers have begun treating independently. For the telehealth component, 123 people were referred, with 62% referred from partner OBOT or CHR sites; 103 (84%) attended a visit, 93 (76%) completed the treatment course, and 61 (50%) have achieved sustained virologic response. Rates of sustained virologic response did not differ by receipt of treatment for opioid use disorder., Conclusions: Providers demonstrated a preference for an in-person training workshop, though further investigation is needed to determine why only a minority of those trained have begun treating HCV independently. The interdisciplinary nature of this program led to efficient treatment of hepatitis C in a real-world population with a majority of patients referred from OBOTs and CHR programs., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Direct acting antivirals (DAAs) have simplified and expanded access to Hepatitis C virus (HCV) treatment. Only 17% of the 2.4 million Americans with HCV have linked to HCV care. We aimed to evaluate linkage to care (LTC) in a non-urban HCV referral clinic with a nurse navigator model and identify disparities in LTC. Methods: A single-center retrospective cohort analysis was performed among all patients referred to an infectious diseases HCV clinic between 2014 and 2018. The primary outcome was LTC, defined as attendance at a clinic appointment. A multivariable Poisson regression model estimated the association of variables with LTC. Results: Among 824 referred patients, 624 (76%) successfully linked to care and 369 (45%) successfully achieved sustained virologic response. Forty-six percent of those referred were uninsured. On multivariable analysis, LTC rates were higher among women (Incidence Rate Ratio [IRR] 1.11, 95% CI 1.03-1.20, p -value = 0.01) and people with cirrhosis (IRR 1.20, 95% CI 1.11-1.30, p -value < 0.001). Lower LTC rates were found for young people (<40 years; IRR 0.88, 95% CI 0.79-0.98, p -value = 0.02) and uninsured people (IRR 0.85, 95% CI 0.77-0.94, p -value = 0.002). Among those without LTC, 10% were incarcerated. Race, proximity to care, substance use, and HIV status were not associated with LTC. Conclusions: Using an embedded nurse navigator model, high LTC rates were achieved despite the prevalence of barriers, including a high uninsured rate. Disparities in LTC based on age, sex, and insurance status are present. Substance use was not associated with LTC. Future interventions to improve care should include expanded access to insurance and programs bridging care for incarcerated populations., (Copyright © 2019 Sherbuk, McManus, Kemp Knick, Canan, Flickinger and Dillingham.)

A retrospective study was conducted to evaluate the value of the antimicrobial stewardship team (AST) combined with infectious diseases consultation (IDC) on management and outcomes of Staphylococcus aureus bacteremia (SAB) in a tertiary-care academic center. Involvement of AST or IDC was associated with reduced mortality of SAB.

Despite ambitious goals to eliminate hepatitis C virus (HCV) in the United States by 2030, the majority of those infected are not aware of their diagnosis, and only a small minority have been cured. A lack of knowledge regarding risk factors and treatment may contribute to low cure rates. We aimed to evaluate HCV knowledge and the association of risk factor knowledge with HCV incidence. In fall 2017, a survey regarding HCV knowledge was disseminated through social media, web link, and in person throughout the state of Virginia. The survey was completed by 613 individuals. Residents of high-incidence counties identified fewer risk factors (5.6 vs 6.1 of 9, p = 0.04), a difference that remained significant when controlling for education and age (p = 0.03). Fewer participants in the high-incidence group recognized snorting drugs to be a risk factor (25% vs 36%, p = 0.01). Only 38% of all respondents correctly identified HCV to be curable. Knowledge of HCV risk factors is lower in high incidence regions. These results identify a critical knowledge gap in the general population at a time of ongoing HCV transmission. Public health interventions must target these gaps in high-incidence regions as part of comprehensive disease prevention programs.

For persons living with HIV and AIDS (PLWHA), care by an HIV-specialist improves outcomes and satisfaction with one's HIV primary care provider (PCP) promotes engagement with care. In the United States, we are facing a workforce shortage of HIV providers. As we aim to train a new generation of HIV providers, it is unclear how PLWHA perceive their experience when cared for by trainees compared to experienced providers. Therefore we assessed patient satisfaction with HIV providers, both trainees in an HIV Primary Care residency program and HIV-specialists. A secondary objective was to evaluate providers' performance in adhering to standard management guidelines for HIV-associated and non-HIV-associated conditions. We surveyed 75 PLWHA, including 51 (68%) assigned to an HIV-specialist PCP and 24 (32%) to a trainee PCP. Overall patient satisfaction on a 10-point scale was similar (mean 9.6 HIV-specialist vs 9.7 trainee, p = 0.71) and remained similar in multivariate logistic regression analysis when controlling for patient age, gender, race, and recently establishing care (Odds Ratio 1.1, 95% Confidence Interval 0.3-5.0). Participants in the trainee group were more likely to feel their provider "always" spent enough time with them (100% vs 81%, p = 0.03). Adherence to HIV guidelines was similar, though trainees were more likely to document counseling on risk reduction (83% vs 47%, p = 0.005) and adherence to antiretroviral therapy (100% vs 66%, p = 0.001). In conclusion, in a structured HIV-training program, residents can provide subspecialty level care in an HIV continuity clinic with levels of performance and patient satisfaction equivalent to those of experienced specialists.

Background: Hepatitis C is now curable for most individuals, and national goals for elimination have been established. Transmission persists, however, particularly in nonurban regions affected by the opioid epidemic. To reach goals of elimination, barriers to treatment must be identified., Methods: In this open cohort of all individuals diagnosed with active hepatitis C from 2010 to 2016 at a large medical center, we identified patient and clinic characteristics associated with our primary outcome, sustained virologic response (SVR). We performed a subgroup analysis for those with documented substance misuse., Results: SVR was achieved in 1544 (41%) of 3790 people with active hepatitis C. In a multivariable Poisson regression model, SVR was more likely in individuals diagnosed outpatient (incident rate ratio [IRR], 1.7; 95% confidence interval [CI], 1.5-2.0), living in close proximity to the medical center (IRR, 1.2; 95% CI, 1.1-1.3), with private insurance (IRR, 1.1; 95% CI, 1.0-1.3), and with cirrhosis (IRR, 1.4; 95% CI, 1.3-1.5). Achieving SVR was less likely in those qualifying as indigent (IRR, 0.8; 95% CI, 0.8-0.9) and those with substance misuse (IRR, 0.8; 95% CI, 0.7-0.9). In the subgroup analysis of those with substance misuse, SVR rates were higher in those linked to the infectious diseases clinic, which has embedded support services, than those linked to the gastroenterology clinic, which does not (IRR, 1.4; 95% CI, 1.1-1.9)., Conclusions: Social determinants of health including proximity to care and poverty impacted achievement of SVR. Those with substance misuse, a high-priority population for treatment of hepatitis C, had better outcomes when receiving care in a clinic with embedded support services.

Background: Chagas cardiomyopathy is a chronic sequela of infection by the parasite, Trypanosoma cruzi. Advanced cardiomyopathy is associated with a high mortality rate, and clinical characteristics have been used to predict mortality risk. Though multiple biomarkers have been associated with Chagas cardiomyopathy, it is unknown how these are related to survival., Objectives: This study aimed to identify biomarkers associated with mortality in individuals with severe Chagas cardiomyopathy in an urban Bolivian hospital., Methods: The population included individuals with and without T. cruzi infection recruited in an urban hospital in Santa Cruz, Bolivia. Baseline characteristics, electrocardiogram findings, medications, and serum cardiac biomarker levels (B-type natriuretic peptide [BNP], N-terminal pro-B-type natriuretic peptide [NT-proBNP], creatine kinase-myocardial band [CK-MB], troponin I, matrix metalloproteinase [MMP]-2, MMP-9, tissue inhibitor of metalloproteinases [TIMP] 1 and 2, transforming growth factor [TGF] beta 1 and 2) were ascertained. Echocardiograms were performed on those with cardiac symptoms or electrocardiogram abnormalities at baseline. Participants were contacted approximately 1 year after initial evaluation; deaths were reported by family members. Receiver-operating characteristic curves (ROC) were used to optimize cutoff values for each marker. For markers with area under the curve (AUC) >0.55, Cox proportional hazards models were performed to determine the hazards ratio (HR) and 95% confidence interval (CI) for the association of each marker with mortality., Results: The median follow-up time was 14.1 months (interquartile range 12.5, 16.7). Of 254 individuals with complete cardiac data, 220 (87%) had follow-up data. Of 50 patients with severe Chagas cardiomyopathy at baseline, 20 (40%) had died. Higher baseline levels of BNP (HR: 3.1, 95% CI: 1.2 to 8.4), NT-proBNP (HR: 4.4, 95% CI: 1.8 to 11.0), CK-MB (HR: 3.3, 95% CI: 1.3 to 8.0), and MMP-2 (HR: 4.2, 95% CI: 1.5 to 11.8) were significantly associated with subsequent mortality., Conclusions: Severe Chagas cardiomyopathy is associated with high short-term mortality. BNP, NT-proBNP, CK-MB, and MMP-2 have added predictive value for mortality, even in the presence of decreased ejection fraction and other clinical signs of congestive heart failure., (Copyright © 2015 World Heart Federation (Geneva). All rights reserved.)

Background: Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc-) individuals., Methods: Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc- groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed., Results: Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities., Conclusions: BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.