Small molecule biomarkers predictive of Chagas disease progression.

Chagas disease (CD) is a neglected tropical disease caused by the parasitic protozoan Trypanosoma cruzi. However, only 20% to 30% of infected individuals will progress to severe symptomatic cardiac manifestations. Current treatments are benznidazole and nifurtimox, which are poorly tolerated regimens. Developing a biomarker to determine the likelihood of patient progression would be helpful for doctors to optimize patient treatment strategies. Such a biomarker would also benefit drug discovery efforts and clinical trials. In this study, we combined untargeted and targeted metabolomics to compare serum samples from T. cruzi-infected individuals who progressed to severe cardiac disease, versus infected individuals who remained at the same disease stage (non-progressors). We identified four unannotated biomarker candidates, which were validated in an independent cohort using both untargeted and targeted analysis techniques. Overall, our findings demonstrate that serum small molecules can predict CD progression, offering potential for clinical monitoring.

In vivo translocator protein in females with autism spectrum disorder: a pilot study.

Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)-a mitochondrial protein-in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [11C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [11C]PBR28 PET-MRI scans. Females with ASD exhibited elevated [11C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [11C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [11C]PBR28 SUVR across time in both groups. Elevated regional [11C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [11C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.

Characterizing Organizational Health Equity Capacity Assessments for Public Health Organizations: A Scoping Review.

OBJECTIVE: Organizational health equity capacity assessments (OCAs) provide a valuable starting point to understand and strengthen an organization's readiness and capacity for health equity. We conducted a scoping review to identify and characterize existing OCAs. METHODS: We searched the PubMed, Embase, and Cochrane databases and practitioner websites to identify peer-reviewed and gray literature articles and tools that measure or assess health equity-related capacity in public health organizations. Seventeen OCAs met the inclusion criteria. We organized primary OCA characteristics and implementation evidence and described them thematically according to key categories. RESULTS: All identified OCAs assessed organizational readiness or capacity for health equity, and many aimed to guide health equity capacity development. The OCAs differed in regard to thematic focus, structure, and intended audience. Implementation evidence was limited. CONCLUSIONS: By providing a synthesis of OCAs, these findings can assist public health organizations in selecting and implementing OCAs to assess, strengthen, and monitor their internal organizational capacity for health equity. This synthesis also fills a knowledge gap for those who may be considering developing similar tools in the future.

Immunologic changes are detectable in the peripheral blood transcriptome of clinically asymptomatic Chagas cardiomyopathy patients.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected parasitic disease that affects approximately 6 million individuals worldwide. Of those infected, 20-30% will go on to develop chronic Chagas cardiomyopathy (CCC), and ultimately many of these individuals will progress to advanced heart failure. The mechanism by which this progression occurs is poorly understood, as few studies have focused on early CCC. In this study, we sought to understand the physiologic changes associated with T. cruzi infection and the development of CCC. We analyzed gene expression in the peripheral blood of asymptomatic Chagas patients with early structural heart disease, Chagas patients without any signs or symptoms of disease, and Chagas-negative patients with and without early structural heart disease. Our analysis shows that early CCC was associated with a downregulation of various peripheral immune response genes, with gene expression changes suggestive of reduced antigen presentation and T cell activation. Notably, these genes and processes were distinct from those of early cardiomyopathy in Chagas-negative patients, suggesting that the processes mediating CCC may be unique from those mediating progression to other cardiomyopathies. This work highlights the importance of the immune response in early CCC, providing insight into the early pathogenesis of this disease. The changes we have identified may serve as biomarkers of progression and could inform strategies for the treatment of CCC in its early stages, before significant cardiac damage has occurred.

Case Report: A Case of Post-Transplant Chagas Reactivation after Negative Trypanosoma cruzi Testing.

Patients with Chagas cardiomyopathy carry a significant risk of reactivation after heart transplantation. Reactivation of Chagas disease can lead to graft failure or systemic complications such as fulminant central nervous system disease and sepsis. As such, careful screening for Chagas seropositivity prior to transplant is crucial to preventing negative outcomes in the post-transplant setting. One challenge in screening these patients is the variety of laboratory tests available and their differing sensitivities and specificities. In this case report, we present a patient who tested positive by a commercial Trypanosoma cruzi antibody assay and later tested negative by CDC confirmatory serological analysis. After the patient underwent orthotopic heart transplant, he underwent protocol-based polymerase chain reaction surveillance for reactivation as a result of persistent concerns for T. cruzi infection. It was discovered shortly thereafter that the patient had reactivation of Chagas disease, confirming that he did have Chagas cardiomyopathy prior to transplantation, despite negative confirmatory testing. This case illustrates the complexities of serological diagnosis of Chagas disease and the importance of additional testing for T. cruzi when the post-test probability remains high even with a commercial, negative serologic test.

The Importance of Screening for Chagas Disease Against the Backdrop of Changing Epidemiology in the USA.

Purpose of Review: This review seeks to identify factors contributing to the changing epidemiology of Chagas disease in the United States of America (US). By showcasing screening programs for Chagas disease that currently exist in endemic and non-endemic settings, we make recommendations for expanding access to Chagas disease diagnosis and care in the US. Recent Findings: Several factors including but not limited to increasing migration, climate change, rapid population growth, growing urbanization, changing transportation patterns, and rising poverty are thought to contribute to changes in the epidemiology of Chagas disease in the US. Outlined are some examples of successful screening programs for Chagas disease in other countries as well as in some areas of the US, notably those which focus on screening high-risk populations and are linked to affordable and effective treatment options. Summary: Given concerns that Chagas disease prevalence and even risk of transmission may be increasing in the US, there is a need for improving detection and treatment of the disease. There are many successful screening programs in place that can be replicated and/or expanded upon in the US. Specifically, we propose integrating Chagas disease into relevant clinical guidelines, particularly in cardiology and obstetrics/gynecology, and using advocacy as a tool to raise awareness of Chagas disease.

Geotemporal analysis of perinatal care changes and maternal mental health: an example from the COVID-19 pandemic.

Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.

Early identification of patients with Chagas disease at risk of developing cardiomyopathy using 2-D speckle tracking strain: Win, Miranda prediction of Chagas cardiomyopathy.

Background: Chagas disease is an endemic protozoan disease with high prevalence in Latin America. Of those infected, 20-30% will develop chronic Chagas cardiomyopathy (CCC) however, prediction using existing clinical criteria remains poor. In this study, we investigated the utility of left ventricular (LV) echocardiographic speckle-tracking global longitudinal strain (GLS) for early detection of CCC. Methods and results: 139 asymptomatic T. cruzi seropositive subjects with normal heart size and normal LV ejection fraction (EF) (stage A or B) were enrolled in this prospective observational study and underwent paired echocardiograms at baseline and 1-year follow-up. Progressors were participants classified as stage C or D at follow-up due to development of symptoms of heart failure, cardiomegaly, or decrease in LVEF. LV GLS was calculated as the average peak systolic strain of 16 LV segments. Measurements were compared between participants who progressed and did not progress by two-sample t-test, and the odds of progression assessed by multivariable logistic regression. Of the 139 participants, 69.8% were female, mean age 55.8 ± 12.5 years, with 12 (8.6%) progressing to Stage C or D at follow-up. Progressors tended to be older, male, with wider QRS duration. LV GLS was -19.0% in progressors vs. -22.4% in non-progressors at baseline, with 71% higher odds of progression per +1% of GLS (adjusted OR 1.71, 95% CI 1.20-2.44, p = 0.003). Conclusion: Baseline LV GLS in participants with CCC stage A or B was predictive of progression within 1-year and may guide timing of clinical follow-up and promote early detection or treatment.

Updated Estimates and Mapping for Prevalence of Chagas Disease among Adults, United States.

We combined American Community Survey data with age-specific Trypanosoma cruzi prevalence derived from US surveys and World Health Organization reports to yield estimates of Chagas disease in the United States, which we mapped at the local level. In addition, we used blood donor data to estimate the relative prevalence of autochthonous T. cruzi infection. Our estimates indicate that 288,000 infected persons, including 57,000 Chagas cardiomyopathy patients and 43,000 infected reproductive-age women, currently live in the United States; 22-108 congenital infections occur annually. We estimated ≈10,000 prevalent cases of locally acquired T. cruzi infection. Mapping shows marked geographic heterogeneity of T. cruzi prevalence and illness. Reliable demographic and geographic data are key to guiding prevention and management of Chagas disease. Population-based surveys in high prevalence areas could improve the evidence base for future estimates. Knowledge of the demographics and geographic distribution of affected persons may aid practitioners in recognizing Chagas disease.

Systematic review of performance-enhancing health worker supervision approaches in low- and middle-income countries.

BACKGROUND: The strength of a health system-and ultimately the health of a population-depends to a large degree on health worker performance. However, insufficient support to build, manage and optimize human resources for health (HRH) in low- and middle-income countries (LMICs) results in inadequate health workforce performance, perpetuating health inequities and low-quality health services. METHODS: The USAID-funded Human Resources for Health in 2030 Program (HRH2030) conducted a systematic review of studies documenting supervision enhancements and approaches that improved health worker performance to highlight components associated with these interventions' effectiveness. Structured by a conceptual framework to classify the inputs, processes, and results, the review assessed 57 supervision studies since 2010 in approximately 29 LMICs. RESULTS: Of the successful supervision approaches described in the 57 studies reviewed, 44 were externally funded pilots, which is a limitation. Thirty focused on community health worker (CHW) programs. Health worker supervision was informed by health system data for 38 approaches (67%) and 22 approaches used continuous quality improvement (QI) (39%). Many successful approaches integrated digital supervision technologies (e.g., SmartPhones, mHealth applications) to support existing data systems and complement other health system activities. Few studies were adapted, scaled, or sustained, limiting reports of cost-effectiveness or impact. CONCLUSION: Building on results from the review, to increase health worker supervision effectiveness we recommend to: integrate evidence-based, QI tools and processes; integrate digital supervision data into supervision processes; increase use of health system information and performance data when planning supervision visits to prioritize lowest-performing areas; scale and replicate successful models across service delivery areas and geographies; expand and institutionalize supervision to reach, prepare, protect, and support frontline health workers, especially during health emergencies; transition and sustain supervision efforts with domestic human and financial resources, including communities, for holistic workforce support. In conclusion, effective health worker supervision is informed by health system data, uses continuous quality improvement (QI), and employs digital technologies integrated into other health system activities and existing data systems to enable a whole system approach. Effective supervision enhancements and innovations should be better integrated, scaled, and sustained within existing systems to improve access to quality health care.

Behavioral coping phenotypes and associated psychosocial outcomes of pregnant and postpartum women during the COVID-19 pandemic.

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic.

Recommendations for Screening and Diagnosis of Chagas Disease in the United States.

BACKGROUND: Chagas disease affects an estimated 326 000-347 000 people in the United States and is severely underdiagnosed. Lack of awareness and clarity regarding screening and diagnosis is a key barrier. This article provides straightforward recommendations, with the goal of simplifying identification and testing of people at risk for US healthcare providers. METHODS: A multidisciplinary working group of clinicians and researchers with expertise in Chagas disease agreed on 6 main questions, and developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, after reviewing the relevant literature on Chagas disease in the United States. RESULTS: Individuals who were born or resided for prolonged time periods in endemic countries of Mexico and Central and South America should be tested for Trypanosoma cruzi infection, and family members of people who test positive should be screened. Women of childbearing age with risk factors and infants born to seropositive mothers deserve special consideration due to the risk of vertical transmission. Diagnostic testing for chronic T. cruzi infection should be conducted using 2 distinct assays. CONCLUSIONS: Increasing provider-directed screening for T. cruzi infection is key to addressing this neglected public health challenge in the United States.

Roadblocks in Chagas disease care in endemic and nonendemic countries: Argentina, Colombia, Spain, and the United States. The NET-Heart project.

BACKGROUND: Chagas disease (CD) is endemic in Latin America; however, its spread to nontropical areas has raised global interest in this condition. Barriers in access to early diagnosis and treatment of both acute and chronic infection and their complications have led to an increasing disease burden outside of Latin America. Our goal was to identify those barriers and to perform an additional analysis of them based on the Inter American Society of Cardiology (SIAC) and the World Heart Federation (WHF) Chagas Roadmap, at a country level in Argentina, Colombia, Spain, and the United States, which serve as representatives of endemic and nonendemic countries. METHODOLOGY AND PRINCIPAL FINDINGS: This is a nonsystematic review of articles published in indexed journals from 1955 to 2021 and of gray literature (local health organizations guidelines, local policies, blogs, and media). We classified barriers to access care as (i) existing difficulties limiting healthcare access; (ii) lack of awareness about CD and its complications; (iii) poor transmission control (vectorial and nonvectorial); (iv) scarce availability of antitrypanosomal drugs; and (v) cultural beliefs and stigma. Region-specific barriers may limit the implementation of roadmaps and require the application of tailored strategies to improve access to appropriate care. CONCLUSIONS: Multiple barriers negatively impact the prognosis of CD. Identification of these roadblocks both nationally and globally is important to guide development of appropriate policies and public health programs to reduce the global burden of this disease.

Cardiovascular biomarkers as predictors of adverse outcomes in chronic Chagas cardiomyopathy.

BACKGROUND: Chronic Chagas Cardiomyopathy (CCM) is a unique form of cardiomyopathy compared to other etiologies of heart failure. In CCM, risk prediction based on biomarkers has not been well-studied. We assessed the prognostic value of a biomarker panel to predict a composite outcome (CO), including the need for heart transplantation, use of left ventricular assist devices, and mortality. METHODS: Prospective cohort study of 100 adults with different stages of CCM. Serum concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), high sensitivity troponin T (hs-cTnT), soluble (sST2), and cystatin-C (Cys-c) were measured. Survival analyses were performed using Cox proportional hazard models. RESULTS: During a median follow-up of 52 months, the mortality rate was 20%, while the CO was observed in 25% of the patients. Four biomarkers (NT-proBNP, hs-cTnT, sST2, and Cys-C) were associated with the CO; concentrations of NT-proBNP and hs-cTnT were associated with the highest AUC (85.1 and 85.8, respectively). Combining these two biomarkers above their selected cut-off values significantly increased risk for the CO (HR 3.18; 95%CI 1.31-7.79). No events were reported in the patients in whom the two biomarkers were under the cut-off values, and when both levels were above cut-off values, the CO was observed in 60.71%. CONCLUSION: The combination of NT-proBNP and hs-TnT above their selected cut-off values is associated with a 3-fold increase in the risk of the composite outcome among CCM patients. The use of cardiac biomarkers may improve prognostic evaluation of patients with CCM.

Recognition and screening for Chagas disease in the USA.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a public health concern, mainly among countries in South and Central America. However, despite the large number of immigrants from endemic countries living in the USA, awareness of CD is poor in the medical community, and therefore it is significantly underdiagnosed. To avoid the catastrophic cardiac complications of CD and to prevent maternal-fetal transmission, widespread educational programs highlighting the need for diagnosis are urgently needed.

Multiple Strokes in a Latin American Patient.

We present a case of a recent immigrant from El Salvador without past medical history who presented to our hospital with symptoms concerning for acute stroke. Brain magnetic resonance imaging (MRI) with gadolinium confirmed an acute stroke along with multiple prior infarcts involving different vascular beds. Head magnetic resonance arteriogram did not reveal any occlusions/stenosis or aneurysmal changes. His subsequent extensive evaluation included an electrocardiogram (ECG) that revealed bifascicular block and echocardiography that suggested an apical aneurysm, but images were limited to assess. To further assess the likelihood of cardiac embolism, he underwent cardiac MRI with gadolinium, which confirmed the apical aneurysm. Because of his country of origin and classic ECG and echo findings, Chagas disease was suspected, and both commercial ELISA and confirmatory ELISA and TESA blots were positive. This is both a classic presentation of Chagas cardiomyopathy and an important reminder that Chagas disease should be considered in the differential diagnosis of cardioembolic stroke in Latin American immigrants from an endemic country.

Contemporary narrative review on left atrial strain mechanics in echocardiography: cardiomyopathy, valvular heart disease and beyond.

Left atrial (LA) strain mechanics refer to the measurement of LA myocardial deformation expressed as a percentage, and have been gathering interest over the last decade with expanding research supporting their utility in multiple cardiovascular disorders. Measured through advanced dynamic imaging techniques which include tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking echocardiography (STE), LA strain mechanics are affected by left ventricular diastolic dysfunction prior to the onset of functional and structural changes in the left ventricle (LV). There is a need for practising cardiologists to become more familiar with the clinical utility of LA strain mechanics. In this article, we begin by reviewing the physiologic function of the LA, using this as a basis for understanding LA strain mechanics. The focus of this review article is to provide a contemporary update on the utility of LA strain mechanics in a range of cardiovascular disorders, including atrial fibrillation (AF), hypertrophic cardiomyopathy (HCM), valvular pathologies, coronary artery disease (CAD) as well as systemic diseases, such as hypertension (HTN), obesity and diabetes mellitus (DM). This article also highlights the current limitations in more widespread clinical applications of LA strain mechanics, as well as outlining the future perspectives on the clinical applications of LA strain mechanics.

Evaluation of 2 Lateral Flow Rapid Tests in the Diagnosis of Chagas Disease in the Washington Metropolitan Area.

We compared the accuracy of the Stat-Pak and Chagas Detect Plus with a latent class analysis. Sensitivity values of 89.7% and 91.9% and specificities of 97.1% and 80.3%, respectively, were seen in the serodiagnosis of Chagas disease in Hispanic immigrants, revealing the limitations of these tests in diverse populations.