Critical analysis of Chagas disease treatment in different countries.

As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In this manuscript, we aim to provide a comparative review of approaches to patients with Chagas disease in the Americas and Europe.

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.

Integration of clinical pharmacists into a heart failure clinic within a safety-net hospital.

BACKGROUND: Management of heart failure with reduced ejection fraction (HFrEF) requires timely initiation and up-titration of guideline-directed medical therapy (GDMT). In safety-net hospitals (SNHs), limited health care staff and resources make achievement of optimal medical therapy challenging. Recent studies have shown that medication titration performed by clinical pharmacists can improve outcomes in ambulatory management of HFrEF; however, the impact of these services within an SNH remains unknown. OBJECTIVE: Determine the impact of integrating clinical pharmacists into a heart failure (HF) clinic on initiation and titration of GDMT within an SNH. METHODS: We performed a single-center retrospective cohort study of patients with HFrEF treated in an ambulatory HF medication titration clinic within an SNH before and after clinical pharmacist integration. Primary outcomes included dose optimization rates of GDMT, time between clinic visits, and time to optimization of GDMT. Exploratory secondary outcomes were all-cause, HF, and cardiovascular acute care service utilization and all-cause, HF, and cardiovascular mortality before and after clinical pharmacist integration up to 6 months after initial clinic visit. RESULTS: A total of 153 patients with HFrEF were treated. Baseline characteristics in the pre- and postintervention groups were comparable. After clinical pharmacist integration, there was a statistically significant improvement in optimization of renin-angiotensin-aldosterone system inhibitor or hydralazine-nitrate equivalent (82% vs. 94%, P = 0.02). Dose optimization rates of beta-blockers (90% vs. 83%, P = 0.22) and mineralocorticoid receptor antagonists (57% vs. 57%, P > 0.99) were unchanged. There was a statistically significant reduction in mean time between clinic visits (26 vs. 14 days, P < 0.001) and in mean time to optimization of GDMT (88 vs. 45 days, P = 0.002). All-cause mortality was reduced (13% vs. 2%, P = 0.01). CONCLUSION: In SNHs, where limited health care staff and resources present as barriers to timely initiation and titration of GDMT, integration of clinical pharmacists into HF clinics can serve as a practical solution.

Critical analysis of Chagas disease treatment in different countries

As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In this manuscript, we aim to provide a comparative review of approaches to patients with Chagas disease in the Americas and Europe.

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.

"You Don't Have a Normal Life": Coping with Chagas Disease in Los Angeles, California.

Chagas disease is the neglected tropical disease of greatest public health impact in the United States, where it affects over 300,000 people. Diverse barriers limit healthcare access for affected people; fewer than 1% have obtained testing or treatment. We interviewed 50 people with Chagas disease in Los Angeles, California, and administered a cultural consensus analysis questionnaire. Participants were asked about their experiences and perceptions of Chagas disease, access to healthcare, and strategies for coping with the disease. In participants' narratives, the physical and emotional impacts of the disease were closely interwoven. Participant explanatory models highlight difficulties in accessing care, despite a desire for biomedical treatment. Obtaining testing and treatment for Chagas disease poses substantial challenges for US patients.

Chagas Disease in the United States: A Perspective on Diagnostic Testing Limitations and Next Steps.

Chagas disease is a neglected tropical disease that affects an estimated 300,000 people in the United States. This perspective piece reviews diagnostic challenges and proposes next steps to address these shortfalls.

COVID-19: Implications for People with Chagas Disease.

As the global COVID-19 pandemic advances, it increasingly impacts those vulnerable populations who already bear a heavy burden of neglected tropical disease. Chagas disease (CD), a neglected parasitic infection, is of particular concern because of its potential to cause cardiac, gastrointestinal, and other complications which could increase susceptibility to COVID-19. The over one million people worldwide with chronic Chagas cardiomyopathy require special consideration because of COVID-19's potential impact on the heart, yet the pandemic also affects treatment provision to people with acute or chronic indeterminate CD. In this document, a follow-up to the WHF-IASC Roadmap on CD, we assess the implications of coinfection with SARS-CoV-2 and Trypanosoma cruzi, the etiological agent of CD. Based on the limited evidence available, we provide preliminary guidance for testing, treatment, and management of patients affected by both diseases, while highlighting emerging healthcare access challenges and future research needs.

COVID-19: Implications for People with Chagas Disease

As the global COVID-19 pandemic advances, it increasingly impacts the vulnerable populations who already bear a heavy burden of neglected tropical diseases. Chagas disease (CD), a neglected parasitic infection, is of particular concern because of its potential to cause cardiac, gastrointestinal, and other complications which could increase susceptibility to COVID-19. The over one million people worldwide with chronic Chagas cardiomyopathy require special consideration because of COVID-19's potential impact on the heart, yet the pandemic also affects treatment provision to people with acute or chronic indeterminate CD. In this document, a follow-up to the WHF-IASC Roadmap on CD, we assess the implications of coinfection with SARS-CoV-2 and Trypanosoma cruzi, the etiological agent of CD. Based on the limited evidence available, we provide preliminary guidance for testing, treatment, and management of patients affected by both diseases, while highlighting emerging healthcare access challenges and future research needs.

The potential economic value of a therapeutic Chagas disease vaccine for pregnant women to prevent congenital transmission.

BACKGROUND: Currently, there are no solutions to prevent congenital transmission of Chagas disease during pregnancy, which affects 1-40% of pregnant women in Latin America and is associated with a 5% transmission risk. With therapeutic vaccines under development, now is the right time to determine the economic value of such a vaccine to prevent congenital transmission. METHODS: We developed a computational decision model that represented the clinical outcomes and diagnostic testing strategies for an infant born to a Chagas-positive woman in Mexico and evaluated the impact of vaccination. RESULTS: Compared to no vaccination, a 25% efficacious vaccine averted 125 [95% uncertainty interval (UI): 122-128] congenital cases, 1.9 (95% UI: 1.6-2.2) infant deaths, and 78 (95% UI: 66-91) DALYs per 10,000 infected pregnant women; a 50% efficacious vaccine averted 251 (95% UI: 248-254) cases, 3.8 (95% UI: 3.6-4.2) deaths, and 160 (95% UI: 148-171) DALYs; and a 75% efficacious vaccine averted 376 (95% UI: 374-378) cases, 5.8 (95% UI: 5.5-6.1) deaths, and 238 (95% UI: 227-249) DALYs. A 25% efficacious vaccine was cost-effective (incremental cost-effectiveness ratio <3× Mexico's gross domestic product per capita, <$29,698/DALY averted) when the vaccine cost ≤$240 and ≤$310 and cost-saving when ≤$10 and ≤$80 from the third-party payer and societal perspectives, respectively. A 50% efficacious vaccine was cost-effective when costing ≤$490 and ≤$615 and cost-saving when ≤$25 and ≤$160, from the third-party payer and societal perspectives, respectively. A 75% efficacious vaccine was cost-effective when ≤$720 and ≤$930 and cost-saving when ≤$40 and ≤$250 from the third-party payer and societal perspectives, respectively. Additionally, 13-42 fewer infants progressed to chronic disease, saving $0.41-$1.21 million to society. CONCLUSION: We delineated the thresholds at which therapeutic vaccination of Chagas-positive pregnant women would be cost-effective and cost-saving, providing economic guidance for decision-makers to consider when developing and bringing such a vaccine to market.

Proposed multidimensional framework for understanding Chagas disease healthcare barriers in the United States.

BACKGROUND: Chagas disease (CD) affects over 300,000 people in the United States, but fewer than 1% have been diagnosed and less than 0.3% have received etiological treatment. This is a significant public health concern because untreated CD can produce fatal complications. What factors prevent people with CD from accessing diagnosis and treatment in a nation with one of the world's most advanced healthcare systems? METHODOLOGY/PRINCIPAL FINDINGS: This analysis of barriers to diagnosis and treatment of CD in the US reflects the opinions of the authors more than a comprehensive discussion of all the available evidence. To enrich our description of barriers, we have conducted an exploratory literature review and cited the experience of the main US clinic providing treatment for CD. We list 34 barriers, which we group into four overlapping dimensions: systemic, comprising gaps in the public health system; structural, originating from political and economic inequalities; clinical, including toxicity of medications and diagnostic challenges; and psychosocial, encompassing fears and stigma. CONCLUSIONS: We propose this multidimensional framework both to explain the persistently low numbers of people with CD who are tested and treated and as a potential basis for organizing a public health response, but we encourage others to improve on our approach or develop alternative frameworks. We further argue that expanding access to diagnosis and treatment of CD in the US means asserting the rights of vulnerable populations to obtain timely, quality healthcare.

Prevalence of Chagas Disease Among Family Members of Previously Diagnosed Patients in Los Angeles, California.

Chagas disease (CD) in the United States is severely underdiagnosed, due to an absence of systematic screening as part of routine healthcare. We screened 189 relatives of 86 existing patients and found a CD prevalence of 7.4%. Screening close relatives of previously diagnosed individuals can effectively identify new CD cases.

Economic value of a therapeutic Chagas vaccine for indeterminate and Chagasic cardiomyopathy patients.

BACKGROUND: Therapeutic vaccines to prevent Chagas disease progression to cardiomyopathy are under development because the only available medications (benznidazole and nifurtimox) are limited by their efficacy, long treatment course, and side effects. Better understanding the potential clinical and economic value of such vaccines can help guide development and implementation. METHODS: We developed a computational Chagas Markov model to evaluate the clinical and economic value of a therapeutic vaccine given in conjunction with benznidazole in indeterminate and chronic Chagas patients. Scenarios explored the vaccine's impact on reducing drug treatment dosage, duration, and adverse events, and risk of disease progression. RESULTS: When administering standard-of-care benznidazole to 1000 indeterminate patients, 148 discontinued treatment and 219 progressed to chronic disease, resulting in 119 Chagas-related deaths and 2293 DALYs, costing $18.9 million in lifetime societal costs. Compared to benznidazole-only, therapeutic vaccination administered with benznidazole (25-75% reduction in standard dose and duration), resulted in 37-111 more patients (of 1000) completing treatment, preventing 11-219 patients from progressing, 6-120 deaths, and 108-2229 DALYs (5-100% progression risk reduction), saving ≤$16,171 per patient. When vaccinating determinate Kuschnir class 1 Chagas patients, 10-197 fewer patients further progressed compared to benznidazole-only, averting 11-228 deaths and 144-3037 DALYs (5-100% progression risk reduction), saving ≤$34,059 per person. When vaccinating Kuschnir class 2 patients, 13-279 fewer progressed (279 with benznidazole-only), averting 13-692 deaths and 283-10,785 DALYs (5-100% progression risk reduction), saving ≤$89,759. Therapeutic vaccination was dominant (saved costs and provided health benefits) with ≥ 5% progression risk reduction, except when only reducing drug treatment regimen and adverse events, but remained cost-effective when costing <$200. CONCLUSIONS: Our study helps outline the thresholds at which a therapeutic Chagas vaccine may be cost-effective (e.g., <5% reduction in preventing cardiac progression, 25% reduction in benznidazole treatment doses and duration) and cost-saving (e.g., ≥5% and 25%, respectively).

Progression of Baseline Electrocardiogram Abnormalities in Chagas Patients Undergoing Antitrypanosomal Treatment.

BACKGROUND: The objective of the study was to better understand the impact of antitrypanosomal treatment on the evolution of Chagas-related, prognostically important electrocardiogram (ECG) abnormalities. METHODS: Initial and posttreatment ECGs were obtained in a prospective cohort of Chagas patients treated with nifurtimox or benznidazole and compared to an untreated cohort. Electrocardiogram disease progression was compared in those with and without baseline abnormalities pre- and posttherapy. RESULTS: Fifty-nine patients were recruited in the treatment arm and followed for an average of 3.9 years. There were no differences between ECG groups with regards to follow-up, age, baseline ejection fraction, or therapy. In the treated cohort, 0 of 30 patients with normal ECGs developed an abnormal ECG compared with 7 of 29 patients with baseline ECG abnormalities who developed new ECG abnormalities (P = .005). In an untreated cohort of 30 patients, 3 of 7 with normal ECGs developed an abnormality compared with 14 of 23 patients with baseline abnormalities (P = .67). Untreated patients had a higher likelihood of developing new EKG abnormalities (56.7% vs 11.9%, P < .001) despite shorter follow-up, and in a multivariate analysis adjusting for baseline EKG status across both treated and untreated cohorts, treated patients were still less likely to have progression of their EKG disease (odds ratio = 0.13, P < .001). The corrected QT (QTc) interval was not significantly affected by either study medication (415 vs 421 ms, initial vs posttreatment QTc; P = .06). CONCLUSIONS: Over an average follow-up of 3.9 years, treated patients with normal baseline ECGs did not have significant changes during a course of treatment; however, those with baseline abnormal ECGs had significant progression of their conduction system disease despite treatment, and those without treatment also experienced a progression of ECG disease. These preliminary results suggest that Chagas patients with normal ejection fraction and normal ECG may benefit the most from antitrypanosomal treatment.

Treatment of Chagas Disease in the United States.

PURPOSE OF REVIEW: Chagas disease (CD) is endemic to much of Latin America, but also present in the United States (U.S.). Following a lengthy asymptomatic period, CD produces serious cardiac or gastrointestinal complications in 30-40% of people. Less than 1% of the estimated six million cases in the Americas, including 326,000-347,000 in the U.S., are diagnosed. Infected persons are typically unaware and the bulk of clinicians are unfamiliar with current treatment guidelines. This review provides U.S. and other clinicians with the latest knowledge of CD treatment. RECENT FINDINGS: Chagas cardiomyopathy (CCM) causes severe fibrosis and autonomic damage in the myocardium. Eliminating the parasite through antitrypanosomal therapy with benznidazole, a nitroimidazole derivative or nifurtimox, a nitrofuran compound, potentially prevents heart failure and other sequelae of advanced CCM. Benznidazole, recently approved by the U.S. Food and Drug Administration (FDA) for children 2-12 years old, is the first-line therapy; optimal dosages are currently being studied. Antitrypanosomal therapy prevents congenital transmission; produces high cure rates for acute, congenital, and early chronic cases; and improves clinical outcomes in adult chronic indeterminate cases. However, this benefit was not observed in a large clinical trial that included patients with advanced CCM. SUMMARY: Treatment with antitrypanosomal drugs can cure CD in acute, congenital, and early chronic cases and provides improved clinical outcomes for chronic indeterminate cases. This treatment should be offered as early as possible, before advanced CCM develops.

"It's Like a Phantom Disease": Patient Perspectives on Access to Treatment for Chagas Disease in the United States.

Chagas disease (CD) affects > 6 million people globally, including > 300,000 in the United States. Although early detection and etiological treatment prevents chronic complications from CD, < 1% of U.S. cases have been diagnosed and treated. This study explores access to etiological treatment from the perspective of patients with CD. In semi-structured interviews with 50 Latin American-born patients of the Center of Excellence for Chagas Disease at the Olive View-UCLA Medical Center, we collected demographic information and asked patients about their experiences managing the disease and accessing treatment. Patients were highly marginalized, with 63.4% living below the U.S. poverty line, 60% lacking a high school education, and only 12% with private insurance coverage. The main barriers to accessing health care for CD were lack of providers, precarious insurance coverage, low provider awareness, transportation difficulties, and limited time off. Increasing access to diagnosis and treatment will not only require a dramatic increase in provider and public education, but also development of programs which are financially, linguistically, politically, and geographically accessible to patients.

A Community-Based Screening Program for Chagas Disease in the USA.

Chagas disease (CD) affects over 300 000 people in the USA, many with limited access to healthcare. Although early detection and treatment prevents life-threatening complications, <1% of people with CD receive diagnosis, and routine screening is virtually nonexistent in the USA. We describe a program that led to an increase in CD screening in the Latin American-born population of Los Angeles.

The Prevalence of Chagas Disease Among Latin American Immigrants with Pacemakers in Los Angeles, California.

AbstractChagas disease (CD), with associated conduction abnormalities, is a common indication for pacemaker implantation in Latin America. The prevalence of CD in Latin American immigrants with pacemakers residing in the United States has never been studied. This single-center cross-sectional study included pacemaker patients who were aged 18 years or more with a previous residence in Latin America for at least 6 months. Patients with an implantable cardioverter-defibrillator, cardiac resynchronization therapy, or iatrogenic and/or congenital heart block were excluded. Serological testing for Trypanosoma cruzi was performed at enrollment. A total of 80 patients were enrolled, and CD was diagnosed in six patients (7.5%). Patients with CD were more likely to be from El Salvador (P = 0.001). Other clinical, therapeutic, electrocardiographic, and echocardiographic variables were similar between the CD and non-CD groups. There is a high prevalence of CD among Latin American immigrants with pacemakers in Los Angeles.