Chagas disease in immunocompromised patients.

SUMMARYAs Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various populations of immunocompromised individuals, including people with HIV and patients undergoing solid organ and hematopoietic stem cell transplantation.

Chagas disease.

Chagas disease persists as a global public health problem due to the high morbidity and mortality burden. Despite the possibility of a cure and advances in transmission control, epidemiological transformations, such as urbanisation and globalisation, and the emerging importance of oral and vertical transmission mean that Chagas disease should be considered an emerging disease, with new cases occurring worldwide. Important barriers to diagnosis, treatment, and care remain, resulting in repressed numbers of reported cases, which in turn leads to inadequate public policies. The validation of new diagnostic tools and treatment options is needed, as existing tools pose serious limitations to access to health care. Integrated models of surveillance, with community and intersectional participation, embedded in the concept of One Health, are essential for control. In addition, mitigation strategies for the main social determinants of health, including difficulties imposed by migration, are important to improve access to comprehensive health care in a globalised scenario.

A Case of Chagas Disease in South Dakota: Diagnosis and Treatment.

Chagas disease is a chronic, systemic parasitic infection caused by the protozoan Trypanosoma cruzi. The primary mode of transmission to humans is by the Reduviid insect, endemic to South America. Recent migration of the vector has led to increased cases in the southern United States and has prompted increased surveillance and blood donation screening. It is unusual to diagnose and treat individuals with Chagas disease in the northern United States. This case describes an immigrant female from El Salvador that was informed she had Chagas disease from a blood bank screening. Confirmation and treatment of the disease were performed by her South Dakota primary care provider thus demonstrating the importance of identifying Chagas disease in the immigrant population in regions where Chagas disease infection is uncommon.

Vector-borne protozoal infections of the CNS: cerebral malaria, sleeping sickness and Chagas disease.

PURPOSE OF REVIEW: Malaria, Chagas Disease and Human African Trypanosomiasis are vector-borne protozoan illnesses, frequently associated with neurological manifestations. Intriguing but ignored, limited mainly to resource-limited, tropical settings, these disorders are now coming to light because of globalisation and improved diagnosis and treatment. Enhanced understanding of these illnesses has prompted this review. RECENT FINDINGS: Methods of diagnosis have currently transitioned from blood smear examinations to immunological assays and molecular methods. Tools to assess neurological involvement, such as magnetic resonance imaging, are now increasingly available in regions and countries with high infection loads. Sleep and other electrophysiological technologies (electroencephalography, actigraphy) are also promising diagnostic tools but requiring field-validation. Access to treatments was formerly limited, even as limitations of agents used in the treatment are increasingly recognised. Newer agents are now being developed and trialled, encouraged by improved understanding of the disorders' molecular underpinnings. SUMMARY: Prompt diagnosis and treatment are crucial in ensuring cure from the infections. Attention should also be due to the development of globally applicable treatment guidelines, the burden of neurological sequelae and elimination of the zoonoses from currently endemic regions.

Current knowledge of Chagas-related heart disease among pediatric cardiologists in the United States.

BACKGROUND: Chagas disease is a pathogenic parasitic infection with approximately 8 million cases worldwide and greater than 300,000 cases in the United States (U.S.). Chagas disease can lead to chronic cardiomyopathy and cardiac complications, with variable cardiac presentations in pediatrics making it difficult to recognize. The purpose of our study is to better understand current knowledge and experience with Chagas related heart disease among pediatric cardiologists in the U.S. METHODS: We prospectively disseminated a 19-question survey to pediatric cardiologists via 3 pediatric cardiology listservs. The survey included questions about demographics, Chagas disease presentation and experience. RESULTS: Of 139 responses, 119 cardiologists treat pediatric patients in the U.S. and were included. Most providers (87%) had not seen a case of Chagas disease in their practice; however, 72% also had never tested for it. The majority of knowledge-based questions about Chagas disease cardiac presentations were answered incorrectly, and 85% of providers expressed discomfort with recognizing cardiac presentations in children. Most respondents selected that they would not include Chagas disease on their differential diagnosis for presentations such as conduction anomalies, myocarditis and/or apical aneurysms, but would be more likely to include it if found in a Latin American immigrant. Of respondents, 87% agreed that they would be likely to attend a Chagas disease-related lecture. CONCLUSIONS: Pediatric cardiologists in the U.S. have seen very few cases of Chagas disease, albeit most have not sent testing or included it in their differential diagnosis. Most individuals agreed that education on Chagas disease would be worth-while.

Artificial Inteligence-Based Decision for the Prediction of Cardioembolism in Patients with Chagas Disease and Ischemic Stroke.

BACKGROUND: Chagas disease (CD) and ischemic stroke (IS) have a close, but poorly understood, association. There is paucity of evidence on the ideal secondary prophylaxis and etiological determination, with few cardioembolic patients being identified. AIMS: This study aimed to describe a multicenter cohort of patients with concomitant CD and IS admitted in tertiary centers and to create a predictive model for cardioembolic embolism in CD and IS. MATERIALS AND METHODS: We retrospectively studied data obtained from electronic medical and regular medical records of patients with CD and IS in several academic, hospital-based, and university hospitals across Brazil. Descriptive analyses of cardioembolic and non-cardioembolic patients were performed. A prediction model for cardioembolism was proposed with 70% of the sample as the derivation sample, and the model was validated in 30% of the sample. RESULTS: A total of 499 patients were analyzed. The median age was similar in both groups; however, patients with cardioembolic embolism were younger and tended to have higher alcoholism, smoking, and death rates. The predictive model for the etiological classification showed close relation with the number of abnormalities detected on echocardiography and electrocardiography as well as with vascular risk factors. CONCLUSIONS: Our results replicate in part those previously published, with a higher prevalence of vascular risk factors and lower median age in patients with cardioembolic etiology. Our new model for predicting cardioembolic etiology can help identify patients with higher recurrence rate and therefore allow an optimized strategy for secondary prophylaxis.

Describing nearly two decades of Chagas disease in Germany and the lessons learned: a retrospective study on screening, detection, diagnosis, and treatment of Trypanosoma cruzi infection from 2000 - 2018.

BACKGROUND: The highly complex and largely neglected Chagas disease (CD) has become a global health problem due to population movements between Latin America and non-endemic countries, as well as non-vectorial transmission routes. Data on CD testing and treatment from routine patient care in Germany of almost two decades was collected and analysed. METHODS: German laboratories offering diagnostics for chronic Trypanosoma cruzi (T. cruzi) infection in routine patient care were identified. All retrievable data on tests performed during the years of 2000-2018 were analysed. Additional clinical information regarding patients diagnosed with CD was collected through questionnaires. RESULTS: Five German laboratories with diagnostics for T. cruzi infection in routine patient care were identified. Centres in Hamburg and Munich offered two independent serological tests to confirm the CD diagnosis, as recommended by WHO during the entire time period 2000-2018. Overall, a total of n = 10,728 independent tests involving n = 5991 individuals were identified with a progressive increase in testing rates over time, only n = 130 (16.0%) of the tested individuals with known nationality came from CD endemic countries. Of all test units conducted at the included institutes, a total of n = 347/10,728 (3.2%) tests on CD were positive, of which n = 200/347 (57.6%) were ELISA, n = 133/347 (38.3%) IFT, n = 10/347 (2.9%) PCR, and n = 4/347 (1.2%) RDT. Of the n = 5991 individuals only n = 81 (1.4%) with chronic infection were identified, n = 52 females and n = 28 males. Additional clinical information could only be collected from n = 47. CONCLUSION: The results of this study give insight into the deployment of screening, detection, diagnosis, and treatment of T. cruzi over the last two decades in Germany and existing deficits therein; the creation of guidelines for Germany could be a step forward to improve the existing gaps.

Chagas disease.

Chagas disease is an anthropozoonosis from the American continent that has spread from its original boundaries through migration. It is caused by the protozoan Trypanosoma cruzi, which was identified in the first decade of the 20th century. Once acute infection resolves, patients can develop chronic disease, which in up to 30-40% of cases is characterised by cardiomyopathy, arrhythmias, megaviscera, and, more rarely, polyneuropathy and stroke. Even after more than a century, many challenges remain unresolved, since epidemiological control and diagnostic, therapeutic, and prognostic methods must be improved. In particular, the efficacy and tolerability profile of therapeutic agents is far from ideal. Furthermore, the population affected is older and more complex (eg, immunosuppressed patients and patients with cancer). Nevertheless, in recent years, our knowledge of Chagas disease has expanded, and the international networking needed to change the course of this deadly disease during the 21st century has begun.

Trypanosoma cruzi Neurotrophic Factor Facilitates Cardiac Repair in a Mouse Model of Chronic Chagas Disease.

Most patients acutely infected with Trypanosoma cruzi undergo short-term structural and functional cardiac alterations that heal without sequelae. By contrast, in patients whose disease progresses to chronic infection, irreversible degenerative chronic Chagas cardiomyopathy (CCC) may develop. To account for the contrast between cardiac regeneration in high-parasitism acute infection and progressive cardiomyopathy in low-parasitism CCC, we hypothesized that T. cruzi expresses repair factors that directly facilitate cardiac regeneration. We investigated, as one such repair factor, the T. cruzi parasite-derived neurotrophic factor (PDNF), known to trigger survival of cardiac myocytes and fibroblasts and upregulate chemokine chemokine C-C motif ligand 2, which promotes migration of regenerative cardiac progenitor cells (CPCs). Using in vivo and in vitro models of Chagas disease, we tested whether T. cruzi PDNF promotes cardiac repair. Quantitative PCR and flow cytometry of heart tissue revealed that stem-cell antigen-1 (Sca-1+) CPCs expand in acute infection in parallel to parasitism. Recombinant PDNF induced survival and expansion of ex vivo CPCs, and intravenous administration of PDNF into naïve mice upregulated mRNA of cardiac stem-cell marker Sca-1. Furthermore, in CCC mice, a 3-week intravenous administration of PDNF protocol induced CPC expansion and reversed left ventricular T-cell accumulation and cardiac remodeling including fibrosis. Compared with CCC vehicle-treated mice, which developed severe atrioventricular block, PDNF-treated mice exhibited reduced frequency and severity of conduction abnormalities. Our findings are in support of the novel concept that T. cruzi uses PDNF to promote mutually beneficial cardiac repair in Chagas disease. This could indicate a possible path to prevention or treatment of CCC.

Travelers' tropical skin diseases: Challenges and interventions.

Tropical regions receive a significant part of the traveling population. It is very important that health professionals are familiar with the main tropical skin diseases and able to advice patients appropriately. This article reviews the main tropical diseases of travelers, with an emphasis on diagnosis, management, and prevention. Among others, cutaneous larva migrans, myiasis, tungiasis, Chagas disease, Dengue fever, African trypanosomiasis, filariasis, and leishmaniasis are discussed. Increasing awareness among travelers and health care professionals can help reduce morbidity and mortality. Continued research on new drugs and vaccines is needed to reduce the risks of tropical diseases.

Chagas disease as example of a reemerging parasite.

Trypanosoma cruzi, the protozoan that causes Chagas disease, is primarily transmitted by three main Triatomine vectors in endemic areas. However, the infection has become a potential emerging disease because the vector is found in non-endemic areas, there is migration of infected asymptomatic people that can infect the vector, become blood donors, or pass the disease vertically (congenital infections). Lastly, the disease can be acquired through contaminated food (oral transmission). This review will present the different transmission pathways, clinical manifestations, diagnostic modalities and treatment considerations of Chagas disease.

Building an innovative Chagas disease program for primary care units, in an urban non- endemic city.

BACKGROUND: On an absolute basis, Argentina is the country with the largest affected population with Chagas Disease (ChD). This constitutes a significant public health issue. As a consequence of Argentina's migratory patterns, there has been a significant increase of affected population in urban centers. An innovative project for early diagnosis and timely treatment of ChD was designed for Municipal Primary Care Facilities of La Plata City, a non- endemic area, in line with a proposal from the Pan-American Health Organization. The project was a public -private intervention. The objectives of this study were to demonstrate the feasibility of the primary healthcare level for early diagnosis and timely treatment of ChD; to design and implement a tailor made program and to innovate in a public-private association. METHODS: The healthcare barriers for early diagnosis and timely treatment for the population with ChD of La Plata were analyzed. The four dimensions described by Peters et al. (Ann N Y Acad Sci 1136:161-71, 2008) were used. The baseline was measured during a previous pilot project and the same items were evaluated at the end of 2017. The model from Damschroder et al. (Implement Sci 4:50, 2009) was used during the implementation process. RESULTS: With all the information gathered during this investigation, a "patient-centered" model was designed. During the program, 17,894 people were serologically tested for ChD, 1,394 were positive and 1,035 were treated. Additionally, 3,750 children from 46 public schools were evaluated for risk factors of ChD. CONCLUSIONS: This project showed the feasibility of the primary healthcare level for early diagnosis and timely treatment of ChD. Tailor made programs and public-private associations should be considered for vulnerable populations in emerging economies in order to enhance efforts and obtain better results. This program may be replicated in other countries of Latin America were Chagas is a main public health issue and, with the corresponding adaptations, for other neglected diseases as well.

Chagas disease: An underrecognized diagnosis.

Chagas disease is a parasite infection primarily transmitted to humans via the bite of triatomine insect vectors. Up to 8 million people are estimated to be infected with Chagas disease in the Americas. Patients who do not receive treatment can develop severe cardiac debility, gastrointestinal organ dysfunction, and may die. The changing demographics of the United States, a consequence of changing immigration patterns, means that healthcare providers are more likely to encounter patients with Chagas disease, and must understand its cause, pathogenesis, diagnosis, and treatment.

Clinical aspects of neurointestinal disease: Pathophysiology, diagnosis, and treatment.

The enteric nervous system (ENS) is involved in the regulation of virtually all gut functions. Conditions referred to as enteric neuropathies are the result of various mechanisms including abnormal development, degeneration or loss of enteric neurons that affect the structure and functional integrity of the ENS. In the past decade, clinical and molecular research has led to important conceptual advances in our knowledge of the pathogenetic mechanisms of these disorders. In this review we consider ENS disorders from a clinical perspective and highlight the advancing knowledge regarding their pathophysiology. We also review current therapies for these diseases and present potential novel reparative approaches for their treatment.

A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2 (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax) using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi), when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFN)γ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi) and the boost (analysis at 180 and 230 dpi). Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO) levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells, preserved the number of IFNγ+ cells, increased the expression of IFNγ mRNA but reduced inducible NO synthase mRNA. Vaccine-based immunostimulation with rAd might offer a rational alternative for re-programming the immune response to preserve and, moreover, recover tissue injury in Chagas' heart disease.

Cell therapies for Chagas disease.

In this review of cell therapies in Chagas disease, we cover aspects related to the disease, its treatment and world demographics, before proceeding to describe the preclinical and clinical trials performed using cell therapies in the search for an alternative therapy for the most severe and lethal form of this disease, chronic chagasic cardiomyopathy.

Overcoming research barriers in Chagas disease-designing effective implementation science.

Chagas disease is a complex tropical parasitic infection. It affects a significant portion of the population in Latin America, especially in areas of poverty and poor access to health care. It also affects immigrants in high-income countries who lack access to health care due to their legal status. Millions of people are at risk of contracting the disease, and approximately 30 % of chronically infected patients will develop cardiomyopathy. The cost of caring for patients that have been infected is substantial. Basic science research has introduced new concepts and knowledge for the parasite and vector biology as well as better understanding of the pathophysiology of the disease. These research findings nevertheless require effective and timely translation into clinical practice. Likewise, the design of new research projects should account for the multiple system-based barriers. Implementation science facilitates the applicability of research findings and identifies barriers to its execution. Creation of implementation science measures to reach and sustain research programs with greater potential to impact Chagas disease are lacking. This point of view proposes opportunities for implementation science in Chagas disease and strategies for researching effective interventions for preventing and treating the disease.

[Strategy to improve access to etiological treatment of Chagas disease at the first level of care in Argentina]. / Estrategia para mejorar el acceso al tratamiento etiológico para la enfermedad de Chagas en el primer nivel de atención en Argentina.

OBJECTIVE: Improve distribution of etiological treatment of Chagas disease by identifying barriers to the decentralization of treatment to the first level of care in Argentina. METHODS: A qualitative, exploratory, and descriptive study was conducted using semi-structured interviews of key actors belonging to the National Chagas Program and members of health teams at the first level of care, for the purpose of identifying barriers to diagnosis and treatment of Chagas disease at different levels (administrative, health agents, and community) that could affect a decentralized distribution strategy. Additionally, pilot decentralization was instituted in 10 primary health care centers in an Argentine province. RESULTS: Semi-structured interviews were conducted with 22 program heads and health professionals. Principal obstacles found were lack of systematic case-finding, poor coordination among levels of care and health system actors, lack of health team training on treatment, patient monitoring, and patient-related barriers. A pilot decentralization program was carried out and strategies were evaluated to optimize large-scale intervention. CONCLUSIONS: The results made it possible to improve implementation of the plan to decentralize treatment through better inter-program coordination, capitalization on existing monitoring and communication tools, and sensitization of health teams. Furthermore, recommendations were developed to improve diagnosis and treatment of Chagas disease.

Health care importance of Treponema pallidum, Chagas' disease and Human immunodeficiency virus 1 among Amerindians of Argentina: an observational study.

The objective of this study was to estimate the prevalence of Treponema pallidum, Trypanosoma cruzi and Human immunodeficiency virus 1 (HIV-1) in five Amerindian populations of Argentina. A retrospective study was conducted among 857 Amerindian populations (112 Kollas, 298 Mbyá-guaraníes, 79 Sagua Huarpes, 368 Wichis) from 2007 to 2010. Screening and confirmation of T. pallidum, T. cruzi and HIV-1 were performed. T. pallidum and T. cruzi infections were detected in all communities with an overall prevalence rate of 4.2% and 16.8%, respectively. Although HIV was not detected, syphilis and Chagas' disease represent a challenge for the health care system and the reinforcement of public health strategies is necessary considering the socioeconomic isolation of these populations.