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.

Analysis of the costs incurred by patients with Chagas disease: The experience in endemic municipalities in Colombia.

BACKGROUND: Out-of-pocket expenditure (OOP) are key costs (medical and non-medical) that many individuals incur to receive health services. They have been identified as a key access barrier for vulnerable populations, in particular for populations affected by neglected diseases with a chronic progression, such as Chagas disease. It is important to understand the costs of accessing healthcare services that are borne by patients with T. cruzi infection. METHODOLOGY: We prepared a structured survey for patients with T. cruzi infection/Chagas disease who were all treated by the healthcare system in endemic municipalities in Colombia. The results were analyzed according to three categories: 1. The socioeconomic profiling of the patients; 2. The costs of accommodation, food and transportation, in addition to the time spent commuting; and 3. the income losses (money that was not earned due to absence from work) related to treatment at the local primary care hospital or at the high-complexity reference hospital. MAIN FINDINGS: Ninety-one patients answered the survey voluntarily. The data revealed that, when treated at the specialized reference hospital, patients spent 5.5 times more on food and accommodation, transportation costs were five times higher, and the loss of earnings was three times higher than when they were treated at the local primary care hospital. Moreover, the amount of time spent on transportation was 4 times higher at the reference hospital. CONCLUSIONS: Providing comprehensive healthcare services for Chagas management at local primary healthcare hospitals would allow the most vulnerable patients to save on expenses related to medical and non-medical costs, in turn leading to higher adhesion to treatment thus benefiting the health system as a whole. These findings are in alignment with the WHO's World Health Assembly 2010 Resolution on the importance of treating Chagas at local primary care hospitals, thereby saving patients time and money, allowing for timely care, and promoting access to healthcare.

Extracellular vesicles from Trypanosoma cruzi-dendritic cell interaction show modulatory properties and confer resistance to lethal infection as a cell-free based therapy strategy.

Extracellular vesicles (EVs) include a heterogeneous group of particles. Microvesicles, apoptotic bodies and exosomes are the most characterized vesicles. They can be distinguished by their size, morphology, origin and molecular composition. To date, increasing studies demonstrate that EVs mediate intercellular communication. EVs reach considerable interest in the scientific community due to their role in diverse processes including antigen-presentation, stimulation of anti-tumoral immune responses, tolerogenic or inflammatory effects. In pathogens, EV shedding is well described in fungi, bacteria, protozoan and helminths parasites. For Trypanosoma cruzi EV liberation and protein composition was previously described. Dendritic cells (DCs), among other cells, are key players promoting the immune response against pathogens and also maintaining self-tolerance. In previous reports we have demonstrate that T. cruzi downregulates DCs immunogenicity in vitro and in vivo. Here we analyze EVs from the in vitro interaction between blood circulating trypomastigotes (Tp) and bone-marrow-derived DCs. We found that Tp incremented the number and the size of EVs in cultures with DCs. EVs displayed some exosome markers and intracellular RNA. Protein analysis demonstrated that the parasite changes the DC protein-EV profile. We observed that EVs from the interaction of Tp-DCs were easily captured by unstimulated-DCs in comparison with EVs from DCs cultured without the parasite, and also modified the activation status of LPS-stimulated DCs. Noteworthy, we found protection in animals treated with EVs-DCs+Tp and challenged with T. cruzi lethal infection. Our goal is to go deep into the molecular characterization of EVs from the DCs-Tp interaction, in order to identify mediators for therapeutic purposes.

Veterinary Chagas Disease (American Trypanosomiasis) in the United States.

Veterinary Chagas disease is a persistent threat to humans, dogs, and other wild or domestic mammals that live where infected triatomine "kissing bug" insect vectors occur across the Americas, including 28 states in the Southern United States. Animals infected with the Trypanosoma cruzi parasite may be asymptomatic or may develop myocarditis, heart failure, and sudden death. It is difficult to prevent animal contact with vectors because they are endemic in sylvatic environments and often disperse to domestic habitats. Challenges for disease management include imperfect diagnostic tests and limited antiparasitic treatment options.

New Insights Into Blue Light Phototherapy in Experimental Trypanosoma cruzi Infection.

The search for an effective etiologic treatment to eliminate Trypanosoma cruzi, the causative agent of Chagas disease, has continued for decades and yielded controversial results. In the 1970s, nifurtimox and benznidazole were introduced for clinical assessment, but factors such as parasite resistance, high cellular toxicity, and efficacy in acute and chronic phases of the infection have been debated even today. This study proposes an innovative strategy to support the controlling of the T. cruzi using blue light phototherapy or blue light-emitting diode (LED) intervention. In in vitro assays, axenic cultures of Y and CL strains of T. cruzi were exposed to 460 nm and 40 µW/cm2 of blue light for 5 days (6 h/day), and parasite replication was evaluated daily. For in vivo experiments, C57BL6 mice were infected with the Y strain of T. cruzi and exposed to 460 nm and 7 µW/cm2 of blue light for 9 days (12 h/day). Parasite count in the blood and cardiac tissue was determined, and plasma interleukin (IL-6), tumoral necrosis factor (TNF), chemokine ligand 2 (CCL2), and IL-10 levels and the morphometry of the cardiac tissue were evaluated. Blue light induced a 50% reduction in T. cruzi (epimastigote forms) replication in vitro after 5 days of exposure. This blue light-mediated parasite control was also observed by the T. cruzi reduction in the blood (trypomastigote forms) and in the cardiac tissue (parasite DNA and amastigote nests) of infected mice. Phototherapy reduced plasma IL-6, TNF and IL-10, but not CCL2, levels in infected animals. This non-chemical therapy reduced the volume density of the heart stroma in the cardiac connective tissue but did not ameliorate the mouse myocarditis, maintaining a predominance of pericellular and perivascular mononuclear inflammatory infiltration with an increase in polymorphonuclear cells. Together, these data highlight, for the first time, the use of blue light therapy to control circulating and tissue forms of T. cruzi. Further investigation would demonstrate the application of this promising and potential complementary strategy for the treatment of Chagas disease.

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.

Chagas Disease across Contexts: Scientific Knowledge in a Globalized World.

Chagas is the most important endemic disease in Latin America. It was progressively constructed as a relevant public issue, starting as a medical problem, focusing later on housing conditions, poverty, or vector agents. In recent decades, research has mainly focused on the parasite's biological characterization. In the meanwhile, both Chagas disease and knowledge about it spread out geographically. We analyze the worldwide scientific production on Chagas, showing that countries' research strategies depend on two main factors: endemicity and research traditions. This approach complements previous studies, allowing us to better understand the construction of Chagas disease as a social and scientific problem.

Tropical Infections in the Context of Kidney Transplantation in Latin America.

Reports on tropical infections among kidney transplant (KT) recipients have increased in recent years, mainly because of the growing number of KT programs located in tropical and subtropical areas, and greater mobility or migration between different areas of the world. Endemic in emerging and developing regions, like most countries in Latin America, tropical infections are an important cause of morbidity and mortality in this population. Tropical infections in KT recipients may exhibit different pathways for acquisition compared with those in nonrecipients, such as transmission through a graft and reactivation of a latent infection triggered by immunosuppression. Clinical presentation may differ compared with that in immunocompetent patients, and there are also particularities in diagnostic aspects, treatment, and prognosis. KT patients must be screened for latent infections and immunized properly. Last, drug-drug interactions between immunosuppressive agents and drugs used to treat tropical infections are an additional challenge in KT patients. In this review, we summarize the management of tropical infections in KT patients.

Enfermedad de Chagas: actualización de un desafío vigente / Chagas disease: update of a current challenge

El objetivo de este artículo de revisión narrativa fue generar un documento de consulta con la información actualizada existente respecto a la Enfermedad de Chagas. La enfermedad de Chagas causada por el protozoo Trypanosoma cruzi, es identificado en la primera década del siglo XX. Seguida a la infección aguda, se puede desarrollar una enfermedad crónica. Hasta en el 30-40% de los casos se caracteriza por miocardiopatía, arritmias y megavísceras. La progresión a la miocardiopatía es devastadoramente rápida y se manifiesta con insuficiencia cardíaca y muerte súbita. Hoy continúa siendo un importante problema de salud pública, no sólo en países endémicos, como consecuencia de la movilidad poblacional entre Latino América, y otros países del mundo.

The objective of this narrative review article was to generate a consultation document with the existing updated information regarding Chagas disease. Chagas disease caused by the protozoan Trypanosoma cruzi, is identified in the first decade of the 20th century. Following acute infection, a chronic disease can develop. In up to 30-40% of cases it is characterized by cardiomyopathy, arrhythmias, and mega viscera. The progression to cardiomyopathy is devastatingly rapid, manifesting with heart failure and sudden death. Today it continues to be an important public health problem, not only in endemic countries, as a consequence of population mobility between Latin America and other countries in the world.

Chagas Congenital Screening in Switzerland: Processes of Recognition and Knowledge-Sharing.

Disparities in control mechanisms to prevent the spread of Chagas disease in Switzerland raise questions about the process of its recognition as a public health problem, particularly as it concerns migrant populations. With a focus on congenital screening practices, I explore the way in which health care providers experience, problematize and respond to the disease, acting as key agents not only in the provision of care but also in the recognition of Chagas disease as a problem that needs to be addressed. Such an approach contributes to the understanding of processes of public health agenda creation around neglected tropical diseases in non-endemic countries.

Making Sense of Chagas Disease among Mexican Immigrants in California.

Mexican immigrants are affected by Chagas disease (CD) in California. It is through the representation of Chagas as a rare disease that participants make sense of the disease. A positive diagnosis has meant the disruption of patients' sense of normality and self-image, as well as their memories of homeland both reproducing and challenging hegemonic and stigmatized ideas of the disease associated with rurality and poverty. Access to treatment and medical care was the major coping mechanism. Health programs on CD should consider the emotional and social impact of the disease on people's self-perceptions to develop better medical care and prevention.

Key Chagas disease missing knowledge among at-risk population in Spain affecting diagnosis and treatment.

BACKGROUND: Chagas disease is endemic in Latin America and, over the last few decades, due to population movements, the disease has spread to other continents. Early diagnosis and treatment are critical in terms of improving outcomes for those living with Chagas disease. However, poor knowledge and awareness is one of barriers that affects access to Chagas disease diagnosis and treatment for the population at risk. Information regarding immigrants' knowledge concerning Chagas disease control and prevention is insufficient in non-endemic countries and, therefore, this study sought to assess Chagas disease knowledge and awareness within the Bolivian community residing in Madrid. METHODS: This cross-sectional study was carried out in March-August 2017. A total of 376 Bolivians answered a structured questionnaire. A knowledge index was created based on respondents' knowledge about transmission, symptoms, diagnosis, and place to seek treatment. Multivariate logistic regressions analyses were performed to assess the factors associated with respondents' knowledge of Chagas disease. RESULTS: A total 159 (42.4%) of Bolivians interviewed about their knowledge of Chagas disease were men and 217 (57.6%) were women. Vinchuca was mentioned as mode of transmission by 71% of the Bolivians surveyed, while only 9% mentioned vertical transmission. Almost half of the Bolivians did not know any symptom of Chagas disease and only 47% knew that a specific blood test is necessary for diagnosis. Most of Bolivians were aware of the severity of Chagas disease, but 45% of Bolivians said that there is no cure for Chagas and 96% did not know any treatment. Based on the index of knowledge generated, only 34% of Bolivians had a good knowledge about Chagas disease transmission, symptoms, diagnosis and treatment. According to the multiple logistic regression analysis, knowledge regarding Chagas disease, diagnosis and treatment was significantly higher amongst older Bolivians who had secondary education at least, as well as amongst those who had already been tested for Chagas disease. CONCLUSIONS: This study found that most of the Bolivian population living in Spain had poor knowledge about Chagas disease transmission, symptoms, diagnostic methods and treatment. A poor understanding of the disease transmission and management is one of the most important barriers when it comes to searching for early diagnosis and appropriate care.

Impacto do déficit de investimentos para o tratamento da doença de chagas no Brasil: revisão narrativa / Impact of the investment deficit for the treatment of chagas disease in Brazil: narrative review / Impacto del déficit de inversión para el tratamiento de la enfermedad de Chagas en Brasil: revisión narrativa

Objetivo: discutir sobre o impacto do déficit de investimentos para o tratamento da Doença de Chagas no Brasil. Método: trata-se de uma revisão narrativa da literatura realizada nas seguintes bases de dados: SCIELO, LILACS, BIREME e MEDLINE. A amostra final foi composta por 27 artigos científicos publicados entre o período de 2000 a 2020. Resultados: o Brasil é um dos países com maior prevalência de pacientes portadores da doença, porém pouco se avançou em pesquisas nessa área, de modo a repercutir em um baixo incentivo e investimento dos governantes e da indústria farmacêutica para a Doença de Chagas, tendo em vista a doença ser de progressão lenta e o diagnóstico e o tratamento serem tardios. Conclusão: fica evidente a falta de investimento e políticas públicas que possibilitem o diagnóstico e o tratamento precoce da doença tendo como conseqüência um déficit na qualidade de vida dos pacientes.(AU)

Objective: to discuss the impact of the investment deficit for the treatment of Chagas Disease in Brazil. Method: This is a narrative review of the literature conducted in the following databases: SCIELO, LILACS, BIREME and MEDLINE. The final sample consisted of 27 scientific articles published between 2000 and 2020. Results: Brazil is one of the countries with the highest prevalence of patients with the disease, but little progress has been made in research in this area, so as to have a low incentive and investment from governments and the pharmaceutical industry for Chagas Disease, in view of the disease being of slow progression and the diagnosis and treatment are late. Conclusion: it is evident the lack of investment and public policies that make possible the diagnosis and early treatment of the disease with the consequence of a deficit in the quality of life of the patients.(AU)

Objetivo: discutir el impacto del déficit de inversión para el tratamiento de la enfermedad de Chagas en Brasil. Método: se trata de una revisión narrativa de la literatura realizada en las siguientes bases de datos: SCIELO, LILACS, BIREME y MEDLINE. La muestra final consistió en 27 artículos científicos publicados entre 2000 y 2020. Resultados: el Brasil es uno de los países con mayor prevalencia de pacientes con la enfermedad, pero se ha avanzado poco en la investigación en esta área, para tener un bajo incentivo e inversión de los gobiernos y de la industria farmacéutica para la enfermedad de Chagas, considerando que la enfermedad es de progresión lenta y el diagnóstico y tratamiento son tardíos. Conclusión: es evidente la falta de inversión y de políticas públicas que permitan el diagnóstico y tratamiento precoz de la enfermedad con el consiguiente déficit en la calidad de vida de los pacientes.(AU)

Multi-criteria decision analysis approach for strategy scale-up with application to Chagas disease management in Bolivia.

OBJECTIVE: Design and build a strategy construction and evaluation software system to help stakeholders to develop viable strategies to expand (and adapt) the Chagas Platform healthcare model through the primary healthcare system in Bolivia. METHODS: The software was built based on a ranking of medical Interventions and Actions (needed to support Interventions' implementation) needed for comprehensive management of Chagas Disease in Bolivia. The ranking was performed using a Multi Criteria Decision Analysis (MCDA) methodology adapted to the WHO's building blocks framework. Data regarding the criteria and the rankings was obtained through surveys and interviews with health care professionals working on Chagas disease. The Analytical Hierarchy Process was used to construct the decision criteria weights. Data Envelopment Analysis was used to identify the Interventions that lay on the efficiency frontier of outcomes and the complexity of associated Actions. These techniques were combined with integer programing tools using the open-source software R to build a decision-making tool to assess the outcomes and complexity of any combination of Interventions and Actions. This model and tool were applied to data concerning the care of Chagas disease in Bolivia collected through surveys of experts. The tool works by loading the data from each specific context. RESULTS: The initial set of Interventions and Actions recommended after analysis of the survey data was further refined through face-to-face interviews with field experts in Bolivia, resulting in a strategy of 18 Interventions and 15 Actions. Within the WHO model the Leadership and Governance building block came up as the one needing more support with Actions such as the inclusion of Chagas into Annual Municipal Operational Plans by appointing local and provincial coordinators. CONCLUSION: This project established the suitability of the model for constructing healthcare strategies. The model could be developed further resulting in a decision-making tool for program managers in a wide range of healthcare related issues, including neglected and/ or prevalent diseases. The tool has the potential to be used at different stages of decision making by diverse stakeholders in order to coordinate activities needed to address a health problem.

"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.

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.