Assessment of the Activity of Nitroisoxazole Derivatives against Trypanosoma cruzi.

The development of new compounds to treat Chagas disease is imperative due to the adverse effects of current drugs and their low efficacy in the chronic phase. This study aims to investigate nitroisoxazole derivatives that produce oxidative stress while modifying the compounds' lipophilicity, affecting their ability to fight trypanosomes. The results indicate that these compounds are more effective against the epimastigote form of T. cruzi, with a 52 ± 4% trypanocidal effect for compound 9. However, they are less effective against the trypomastigote form, with a 15 ± 3% trypanocidal effect. Additionally, compound 11 interacts with a higher number of amino acid residues within the active site of the enzyme cruzipain. Furthermore, it was also found that the presence of a nitro group allows for the generation of free radicals; likewise, the large size of the compound enables increased interaction with aminoacidic residues in the active site of cruzipain, contributing to trypanocidal activity. This activity depends on the size and lipophilicity of the compounds. The study recommends exploring new compounds based on the nitroisoxazole skeleton, with larger substituents and lipophilicity to enhance their trypanocidal activity.

Knowledge, Attitudes and Practices of Chagas a Neglected Tropical Disease in Rural Communities of the Colombian Caribbean, CHAGCOV Study.

PURPOSE: Chagas disease (CD) a Neglected Tropical Diseases is an important public health issue in countries where is still endemic, included in the Sustainable Development Goals (SDG). Traditionally restricted to rural areas with diverse routes of transmissions from vectorial to oral with acute manifestations but being more common diagnosed in chronic stages. The aim of this investigation was to characterize the Knowledge, Attitudes and Practices (KAP) related to Chagas disease (CD) in two rural settlements of the Colombian Caribbean with previous records of the disease and/or the parasite. METHODS: A cross-sectional descriptive study was made in two rural settlements in Colombia and surveillance instrument was developed to measure Knowledge, Attitudes and Practices (KAP) related to Chagas disease (CD). RESULTS: In a population with > 60% women and access to social security around 66.5%; 81,6% were homeowners with access to water and electricity > 90% but only 9% of sewerage. The level of knowledge about CD was around 62% but lack of specificity about comprehension of transmission routes (74,6%), and symptoms (85,3%) were found; concluding that 86% of the surveyed sample had very poor level of knowledge about the disease despite preventive campaigns carried out in the two communities studied. CONCLUSIONS: Despite of a low frequency of CD in this Caribbean areas, the presence of vector, risk factors plus poor level of knowledge about the disease justify that public health intervention strategies should be implemented and monitored over time to maintain uninterrupted surveillance of Chagas Disease.

Optimization of benzenesulfonyl derivatives as anti-Trypanosomatidae agents: Structural design, synthesis, and pharmacological assessment against Trypanosoma cruzi and Leishmania infantum.

Leishmaniasis and Chagas disease are neglected tropical diseases caused by Trypanosomatidae parasites. Given the numerous limitations associated with current treatments, such as extended treatment duration, variable efficacy, and severe side effects, there is an urgent imperative to explore novel therapeutic options. This study details the early stages of hit-to-lead optimization for a benzenesulfonyl derivative, denoted as initial hit, against Trypanossoma cruzi (T. cruzi), Leishmania infantum (L. infantum) and Leishmania braziliensis (L. braziliensis). We investigated structure - activity relationships using a series of 26 newly designed derivatives, ultimately yielding potential lead candidates with potent low-micromolar and sub-micromolar activities against T. cruzi and Leishmania spp, respectively, and low in vitro cytotoxicity against mammalian cells. These discoveries emphasize the significant promise of this chemical class in the fight against Chagas disease and leishmaniasis.

Assessment of health-related quality of life in patients with Chagas cardiomyopathy using Minnesota living with heart failure questionnaire: A validation study.

OBJECTIVE: Chagas cardiomyopathy (ChC) is the most severe clinical form of Chagas disease and, in association with psychosocial factors, can compromise the health-related quality of life (HRQoL) of affected patients. To date, there is no specific instrument to assess the HRQoL of these patients, and the Minnesota Living with Heart Failure Questionnaire (MLwHFQ), specific for heart failure, is being used both in research and current clinical practice. Therefore, we aimed to verify the validity of the MLwHFQ in the assessment of HRQoL of patients with ChC. METHODS: Fifty patients with ChC (50.6 ± 10.1 years, NYHA I-III) were evaluated. The MLwHFQ, Short-Form of Health Survey (SF-36), Beck Depression Inventory (BDI), and Human Activity Profile (HAP) were applied. All patients underwent echocardiography and Cardiopulmonary Exercise Testing (CPET). RESULTS: The MLwHFQ score correlated with almost all SF-36 domains (with r-value ranging from -0.38 to -0.69), except pain (p = 0.118). The MLwHFQ score also correlated with the BDI score (r = 0.748; p < 0.001), HAP score (r = -0.558; p = 0.001), peak oxygen uptake (r = -0.352; p = 0.01), and left ventricular ejection fraction (r = -0.329; p = 0.021). There was no significant difference in the score found on the MLwHFQ among NYHA classes (p = 0.101), as well as between patients with systolic dysfunction (n = 30) and preserved cardiac function (n = 20) (p = 0.058). Similarly, there was no significant difference in the score found on the physical (p = 0.423) and mental (p = 0.858) components of SF-36 between patients with systolic dysfunction and preserved cardiac function (p = 0.271 and p = 0.609, respectively). There was also no difference in the mental component of SF-36 among NYHA classes (p = 0.673). However, the HRQoL using the physical component of SF-36 was worse in advanced NYHA classes (p = 0.014). CONCLUSION: MLwHF correlated with most SF-36 HRQoL domains, depressive symptoms, physical activity, and systolic function and seems to be valid in assessing the HRQoL of ChC patients.

Survival analysis of Chagas disease patients, beneficiaries of social security and social assistance in Brazil, 1942-2016 / Análise de sobrevida de portadores da doença de Chagas, beneficiários da previdência e da assistência social no Brasil, 1942-2016

ABSTRACT Objective To analyze the survival of patients with Chagas disease, beneficiaries of social security and social assistance, in Brazil, from 1942 to 2016. Methods This is a retrospective cohort study with data from the Brazilian Ministry of Social Security. The event of interest was death, and the survival functions were estimated by the Kaplan-Meier and Cox regression methods. Results In the period "onset of the disease until death", women (HR=0.54; 95%CI 0.43-0.53) and receiving social security benefits (HR=0.13; 95%CI 0.11-0.23) were associated with longer survival. Lower survival was associated with the cardiac form of the disease (HR=2.64; 95%CI 2.23-3.12), living in a rural area (HR=1.23; 95%CI 1.14-1.21), and manifestation of the disease between the years 2000 and 2016 (HR=5.32; 95%CI 4.74-5.93). Likewise, in the period "work disability until death", women (HR=0.51; 95%CI 0.41-0.52) and receiving social security benefits (HR=0.24; 95%CI 0,14-0.45) were associated with longer survival, as well as the cardiac form of the disease (HR=1.95; 95%CI 1.83-2.13), living in a rural area (HR=1.31; 95%CI 1.21-1.54), and manifestation of the disease between 2000 and 2016 (HR=1.53; 95%CI 1.33-1.71) were associated with lower survival. Conclusion The main predictors of mortality and survival of patients with Chagas disease who receive social security and assistance benefits in Brazil were presented. These findings can guide the definition of priorities for follow-up actions by Primary Health Care, currently recommended for the longitudinal management of the disease.

RESUMO Objetivo Analisar a sobrevida de portadores da doença de Chagas, beneficiários da previdência e da assistência social no Brasil, 1942-2016. Métodos Estudo de coorte retrospectivo com dados do Ministério da Previdência Social. O evento de interesse foi o óbito, e as funções de sobrevida foram estimadas pelos métodos Kaplan-Meier e de regressão de Cox. Resultados No período "início da doença até o óbito", o sexo feminino (HR=0,54; IC95% 0,43-0,53) e recebimento de benefícios previdenciários (HR=0,13; IC95% 0,11-0,23) foram associados a maior sobrevida. A menor sobrevida esteve associada à forma cardíaca da doença (HR=2,64; IC95% 2,23-3,12), residência em zona rural (HR=1,23; IC95% 1,14-1,21) e manifestação da doença entre os anos de 2000 e 2016 (HR=5,32; IC95% 4,74-5,93). Da mesma forma, no período "incapacidade laboral até o óbito", o sexo feminino (HR=0,51; IC95% 0,41-0,52) e o recebimento de benefícios previdenciários (HR=0,24; IC95% 0,14-0,45) foram associados a maior sobrevida, assim como forma cardíaca da doença (HR=1,95; IC95% 1,83-2,13), residência em zona rural (HR=1,31; IC95% 1,21-1,54) e manifestação da doença entre os anos de 2000 e 2016 (HR=1,53; IC95% 1,33-1,71) associaram-se a menor sobrevida. Conclusão Os principais preditores de mortalidade e sobrevida de portadores de doença de Chagas que recebem benefícios previdenciários e assistenciais no Brasil foram apresentados. Estes achados podem nortear a definição de prioridades de ações de acompanhamento pela atenção primária à saúde, preconizada atualmente para o manejo longitudinal da doença.

Assessment of Community Awareness and Screening of Chagas Disease in the Latin American Community of Greater New Orleans.

Chagas disease is a public health problem in the Americas, from the southern United States (USA) to Argentina. In the USA, less than 1% of domestic cases have been identified and less than 0.3% of total cases have received treatment. Little is known about affected immigrant Latin American communities. A prospective study was conducted to assess knowledge about Chagas disease among the Latin American community living in the Greater New Orleans area. Participants answered a baseline questionnaire, viewed a short educational video presentation, completed a post-presentation questionnaire, and were screened with an FDA-approved blood rapid diagnostic test (RDT). A total of 154 participants from 18 Latin American countries (n = 138) and the USA (n = 16) were enrolled and screened for Trypanosoma cruzi infection. At baseline, 57% of the participants knew that Chagas disease is transmitted through an insect vector, and 26% recognized images of the vector. Following the administration of an educational intervention, the participants' knowledge regarding vector transmission increased to 91% and 35% of participants were able to successfully identify images of the vector. Five participants screened positive for T. cruzi infection, indicating a 3.24% [95%CI: 1.1-7.5%] prevalence of Trypanosoma cruzi infection within the Latin American community of the New Orleans area. Results highlight the urgent need for improving access to education and diagnostics of Chagas disease.

Assessment of Cross-Reactivity of Chimeric Trypanosoma cruzi Antigens with Crithidia sp. LVH-60A: Implications for Accurate Diagnostics.

This study focuses on developing accurate immunoassays for diagnosing Chagas disease (CD), a challenging task due to antigenic similarities between Trypanosoma cruzi and other parasites, leading to cross-reactivity. To address this challenge, chimeric recombinant T. cruzi antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) were synthesized to enhance specificity and reduce cross-reactivity in tests. While these antigens showed minimal cross-reactivity with leishmaniasis, their performance with other trypanosomatid infections was unclear. This study aimed to assess the diagnostic potential of these IBMP antigens for detecting CD in patients with Crithidia sp. LVH-60A, a parasite linked to visceral leishmaniasis-like symptoms in Brazil. This study involved seven Crithidia sp. LVH-60A patients and three Leishmania infantum patients. The results indicated that these IBMP antigens displayed 100% sensitivity, with specificity ranging from 87.5% to 100%, and accuracy values between 90% and 100%. No cross-reactivity was observed with Crithidia sp. LVH-60A, and only one L. infantum-positive sample showed limited cross-reactivity with IBMP-8.1. This study suggests that IBMP antigens offer promising diagnostic performance, with minimal cross-reactivity in regions where T. cruzi and other trypanosomatids are prevalent. However, further research with a larger number of Crithidia sp. LVH-60A-positive samples is needed to comprehensively evaluate antigen cross-reactivity.

From serological surveys to disease burden: a modelling pipeline for Chagas disease.

In 2012, the World Health Organization (WHO) set the elimination of Chagas disease intradomiciliary vectorial transmission as a goal by 2020. After a decade, some progress has been made, but the new 2021-2030 WHO roadmap has set even more ambitious targets. Innovative and robust modelling methods are required to monitor progress towards these goals. We present a modelling pipeline using local seroprevalence data to obtain national disease burden estimates by disease stage. Firstly, local seroprevalence information is used to estimate spatio-temporal trends in the Force-of-Infection (FoI). FoI estimates are then used to predict such trends across larger and fine-scale geographical areas. Finally, predicted FoI values are used to estimate disease burden based on a disease progression model. Using Colombia as a case study, we estimated that the number of infected people would reach 506 000 (95% credible interval (CrI) = 395 000-648 000) in 2020 with a 1.0% (95%CrI = 0.8-1.3%) prevalence in the general population and 2400 (95%CrI = 1900-3400) deaths (approx. 0.5% of those infected). The interplay between a decrease in infection exposure (FoI and relative proportion of acute cases) was overcompensated by a large increase in population size and gradual population ageing, leading to an increase in the absolute number of Chagas disease cases over time. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

In silico and in vitro assessment of anti-Trypanosoma cruzi efficacy, genotoxicity and pharmacokinetics of pentasubstituted pyrrolic Atorvastatin-aminoquinoline hybrid compounds.

Atorvastatin (AVA) is a third-generation statin with several pleiotropic effects, considered the last synthetic pharmaceutical blockbuster. Recently, our group described the effects of AVA on DNA damage prevention and against Trypanosoma cruzi infection. In this study, our aim was to evaluate the efficacy, safety, and in silico pharmacokinetic profile of four hybrids of aminoquinolines with AVA 4a-d against T. cruzi using in vitro and in silico models. These synthetic compounds were designed by hybridization of the pentapyrrolic moiety of AVA with the aminoquinolinic unit of chloroquine or primaquine. Pharmacokinetics (ADME) and toxicity parameters were predicted by SwissADME, admetSAR and LAZAR in silico algorithms. The trypanocidal activity of AVA-quinoline hybrids were evaluated in vitro against amastigotes and trypomastigotes of T. cruzi, from Y (Tc II) and Tulahuen (Tc VI) strains. In vitro cardiocytotoxicity was assessed using primary cultures of mouse embryonic cardiac cells and in vitro hepatocytotoxicity on bidimensional and 3D-cultured HepG2 cells. Genotoxicity was evaluated by Ames test and micronucleus assay. Despite the overall good in silico ADMET profile, all tested compounds were predicted to be hepatotoxic. All hybrid derivatives presented high trypanocidal activity, against both trypomastigote and intracellular forms of T. cruzi, presenting EC50's lower than 1 µM besides superior selectivity than the reference drug, without evidences of cardiotoxicity in vitro. The compounds 4a and 4b presented a time-dependent toxicity in monolayer culture of HepG2 but no detectable toxic effects in their spheroids, opposing to the in silico prediction. We can conclude that the AVA-aminoquinoline hybrids presented a hit profile as antiparasitic agents in synthetic pharmaceutical innovation platforms.

Analysis of the Chagas disease situation in Japan: a cross sectional study and cost-effectiveness analysis of a Chagas disease screening program.

Background: Japan is estimated to host 3000 cases of Chagas disease (CD). However, there are no epidemiological data and policies for prevention and care. We aimed to analyze the current situation of CD in Japan and identify possible barriers to seeking care. Methods: This cross-sectional study included Latin American (LA) migrants living in Japan from March 2019 to October 2020. We obtained blood samples to identify participants infected with Trypanosoma cruzi, and data about sociodemographic information, CD risk factors, and barriers to access to the Japanese national health care system (JNHS). We used the observed prevalence to calculate the cost-effectiveness analysis of the screening of CD in the JNHS. Findings: The study included 428 participants, most of them were from Brazil, Bolivia and Peru. The observed prevalence was 1.6% (expected prevalence= 0.75%) and 5.3% among Bolivians. Factors associated with seropositivity were being born in Bolivia, having previously taken a CD test, witnessing the triatome bug at home, and having a relative with CD. The screening model was more cost-effective than the non-screening model from a health care perspective (ICER=200,320 JPY). Factors associated with access to JNHS were being female, length of stay in Japan, Japanese communication skills, source of information, and satisfaction about the JNHS. Interpretation: Screening of asymptomatic adults at risk of CD may be a cost-effective strategy in Japan. However, its implementation should consider the barriers that affect LA migrants in access to the JNHS. Funding: Nagasaki University and Infectious Diseases Japanese Association.

Development of vaccines for Chagas disease (CRUZIVAX): stakeholders' preferences and potential impacts on healthcare.

A vaccine for Chagas disease does not currently exist. This study aims to inform the development of two vaccines for the prevention and treatment of Trypanosoma cruzi infection, and guide their pre-clinical phase up to clinical phase I. The three main objectives are: 1) to explore patients' and policy makers' preferences on the candidate vaccines in Argentina and Spain; 2) to investigate health-related quality of life of patients affected by Chagas disease; and 3) to assess the potential health provider savings associated with the vaccines, in terms of resource use and health care costs. Discrete choice experiments will be employed to estimate and characterize the theoretical demand for the vaccines and investigate patients' and policy makers' preferences. Health-related quality of life will be assessed using the EQ-5D-3L questionnaire. Resources use and costs associated with Chagas disease will be investigated using information from the databases of the Hospital Clínic of Barcelona.

External quality assessment of the entomological identification of triatomines in the network of public laboratories in Rondônia, Brazil

ABSTRACT Background: An external quality assessment on the identification of triatomines within the laboratory network in the state of Rondônia. Methods: Seven laboratories participated in this evaluation. Each was provided with support materials and nine insects from the Hemiptera order for identification. Results: All samples were accurately identified at the species level. However, correct sex identification was achieved for only 79% of the samples. The most significant challenges were encountered in determining the sex of predators, phytophagous species, Rhodnius robustus, and Rhodnius pictipes. Conclusions: The identified shortcomings can inform enhancements in vector control programs for Chagas disease.

¿Por qué todos los técnicos de campo del Programa Nacional de Chagas de Argentina son varones? / Why all the field technicians of the National Chagas Program in Argentina are men? / Por que todos os técnicos de campo do Programa Nacional de Chagas na Argentina são homens?

Resumen El Chagas es una enfermedad causada por el parásito Trypanosoma cruzi y una problemática de salud socioambiental presente en todo el mundo. Una de las vías de transmisión de este parásito es a través del contacto con heces de vinchucas infectadas. En Argentina existen programas de control vectorial que se encargan de prevenir esta vía de transmisión. Específicamente quienes realizan este trabajo son los técnicos de campo, que son prácticamente todos varones. Mediante un abordaje cualitativo e interpretativo que incluyó entrevistas, análisis documental y observación, indagamos por qué las mujeres no se desarrollan en esta área ocupacional dentro del Programa Nacional de Chagas. La mayoría de las personas entrevistadas justificaron la falta de contratación de mujeres basándose en estereotipos de género. Otro gran grupo indicó que se debe al posible daño que los insecticidas les generarían. Sin embargo, no existen recomendaciones ni reglamentaciones oficiales que demuestren que las mujeres no deban realizar este tipo de trabajo, por lo que concluimos que se trata de un acto discriminatorio por género hacia ellas. Consideramos que es necesario que los equipos de trabajo sean diversos en cuanto a género, ya que podrían mejorar las intervenciones y estrategias de control vectorial en los diferentes territorios.

Abstract Chagas is a disease caused by the parasite Trypanosoma cruzi and a socio-environmental health problem present throughout the world. One of the routes of transmission of this parasite is through contact with feces of infected kissing bugs. In Argentina there are vector control programs that are responsible for preventing this route of transmission. Specifically, those who are in charge of this work are the field technicians, who are practically all men. Through a qualitative and interpretive approach that included interviews, documentary analysis and observation, we investigated why women do not participate in this occupational area in the National Program of Chagas. Most of the people interviewed justified the lack of women based on gender stereotypes. Another group indicated that it is due to the possible damage that insecticides would generate in women. We found that there is occupational segregation by gender towards women and other sex-gender identities, since there are no official recommendations or regulations which forbids women to perform in this type of job. We believe that it is necessary for the work teams to be diverse in terms of gender, since it would improve vector control interventions and strategies in the different territories.

Resumo A doença de Chagas é um problema de saúde socioambiental presente em todo o mundo. Uma das vias de transmissão é através do contato com fezes de barbeiros infectados com o parasita Trypanosoma cruzi. Na Argentina existem programas de controle de vetores que previnem esta forma de transmissão. Especificamente, os responsáveis por este trabalho são os técnicos de campo, que praticamente são todos homens. Neste estudo, procuramos encontrar respostas sobre porque as mulheres não participam dessa área ocupacional no Programa Nacional de Chagas por meio de uma abordagem qualitativa e interpretativa que incluiu entrevistas, análise documental e observação. A maioria das pessoas entrevistadas justificou a falta de mulheres com base em estereótipos de gênero. Outro grupo indicou que é devido ao possível dano que os inseticidas lhes causariam. No entanto, não existem recomendações ou regulamentos oficiais que demonstrem que as mulheres não devem exercer este tipo de trabalho, pelo que concluímos que se trata de um ato discriminatório com base no gênero em relação a elas. Acreditamos que é necessário que as equipes de trabalho sejam diversificadas em termos de gênero, pois isso melhoraria as intervenções e estratégias de controle de vetores nos diferentes territórios.

Sustained monomorphic ventricular tachycardia as the presenting sign of Chagas' cardiomyopathy in a low prevalence setting, diagnosis and management challenges. A case report.

Approximately 300,000 people in the United States are estimated to have Chagas' disease, with cardiac manifestations including arrhythmias occurring in 20%-30% of patients. We report a patient diagnosed with Chagas' cardiomyopathy after presenting in ventricular tachycardia. This patient was asymptomatic before her presentation with recurrent episodes of ventricular tachycardia, which motivated us to screen her since she was an immigrant from an endemic Chagas region. This manuscript highlights some of the characteristic cardiac magnetic resonance imaging (MRI) and electrophysiology findings present in patients with Chagas' cardiomyopathy. We also detail the management of patients with Chagas' cardiomyopathy who have suffered from ventricular tachycardia.

Global, Regional, and National Trends of Chagas Disease from 1990 to 2019: Comprehensive Analysis of the Global Burden of Disease Study.

Background: Chagas disease (CD) is a neglected tropical disease, endemic in Latin America, but due to migration and environmental changes it has become a global public health issue. Objectives: To assess the global prevalence and disability-adjusted life years due to CD using findings from the Global Burden of Disease Study 2019. Methods: The Global Burden of Disease data was obtained from the Global Burden of Disease Collaborative Network; results were provided by the Institute for Health Metrics and Evaluation. The prevalence and disability-adjusted life-years (DALYs) were described at a global, regional, and national level, including data from 1990 to 2019. Results: Globally, CD prevalence decreased by 11.3% during the study period, from 7,292,889 cases estimated in 1990 to 6,469,283 in 2019. Moreover, the global DALY rate of CD decreased by 23.7% during the evaluated period, from 360,872 in 1990 to 275,377 in 2019. In addition, significant differences in the burden by sex, being men the most affected, age, with the elderly having the highest burden of the disease, and sociodemographic index (SDI), with countries with the lowest SDI values having the highest prevalence of the disease, were observed. Finally, the prevalence trends have followed different patterns according to the region, with a sustained decrease in Latin America, compared to an increasing trend in North America and Europe until 2010. Conclusion: The global burden of CD has changed in recent decades, with a sustained decline in the number of cases. Although the majority of cases remain concentrated in Latin America, the increase observed in countries in North America and Europe highlights the importance of screening at-risk populations and raising awareness of this neglected tropical disease.

Comparison of 1-year healthcare resource utilization and related costs for patients with heart failure in the Chagas and non-Chagas matched cohorts.

Background: Chagas disease is one of the leading causes of heart failure (HF) in Latin Americans, and there are limited data available that examine related costs of care for patients with HF. This study aimed to compare healthcare resource utilization and related costs for patients with HF, with and without Chagas disease. Methods: A prospective matched-cohort study comparing the healthcare costs for patients with HF with Chagas disease and care costs for patients with HF without Chagas disease was conducted between January 2019 and December 2019. Only direct costs have been estimated, including hospitalization costs, medications and other cardiovascular interventions, and clinical and laboratory follow-up for up to 1 year. Results: A total of 80 patients with chronic HF were included in the study. Of the 80 patients, 40 patients in the Chagas cohort and 40 patients in the non-Chagas cohort were matched for age, insurer and sex. From a social security system perspective, the total costs for the two cohorts during the study period were U$970,136. Specifically, the healthcare costs for the Chagas cohort were greater than the total healthcare costs for the non-Chagas group (U$511,931 versus U$458,205; p = 0.6183) Most costs were associated with hospitalizations (65.5% versus 59.6%), with averages of U$12,798.5 and U$11,455.1 per person in the Chagas and non-Chagas groups, respectively. In both the Chagas (51.6%) and non-Chagas cohorts (54.5%), causes of readmission unrelated to HF outweighed causes of readmission related to HF. High incidences of hospital admissions were observed during the rainy (cold) season for both cohorts. Conclusions: Over a 12-month follow-up period, patients with chronic HF and Chagas consume as many healthcare resources as those with chronic HF and without Chagas. These data highlight the considerable and growing economic burden of HF on the Colombian health system.

Cost-effectiveness of an exercise-based cardiovascular rehabilitation program in patients with chronic Chagas cardiomyopathy in Brazil: An analysis from the PEACH study.

OBJECTIVES: The present study aimed to perform a cost-effectiveness analysis of an exercise-based cardiovascular rehabilitation (CR) program in patients with chronic Chagas cardiomyopathy (CCC). METHODS: Cost-effectiveness analysis alongside a randomised clinical trial evaluating the effects of a 6-month exercise-based CR program. The intervention group underwent 3 weekly exercise sessions. The variation of peak oxygen consumption (VO2peak ) was used as a measurement of clinical outcome. Cost information from all healthcare expenses (examinations, healthcare visits, medication and hospitalisation) were obtained from the medical records in Brazilian reais (R$) and transformed into dollars using the purchasing power parity ($PPP). The longitudinal costs variation was evaluated through linear mixed models, represented by ß coefficient, adjusted for the baseline values of the dependent variable. The cost-effectiveness evaluation was determined through an incremental cost-effectiveness ratio using the HEABS package (Stata 15.0). RESULTS: The intervention group presented higher costs with healthcare visits (ß = +3317.3; p < 0.001), hospitalisation (ß = +2810.4; p = 0.02) and total cost (ß = +6407.9; p < 0.001) after 3 months of follow-up. Costs related to healthcare visits (ß = +2455.8; p < 0.001) and total cost (ß = +4711.4; p < 0.001) remained higher in the intervention group after 6 months. The CR program showed an incremental cost-effectiveness ratio (ICER) of $PPP 1874.3 for each increase of 1.0 ml kg-1  min-1 of VO2peak . CONCLUSIONS: The CR program can be considered a cost-effective alternative and should be included as an intervention strategy in the care of patients with CCC.

Assessment of a combined treatment with a therapeutic vaccine and benznidazole for the Trypanosoma cruzi chronic infection.

The difficulties encountered in achieving treatments for chronic Chagas disease have promoted the investigation of new therapeutic strategies. In this study, we used two murine models of Trypanosoma cruzi chronic infection to determine the usefulness of applying a therapeutic vaccine alone or followed by benznidazole (Bz) chemotherapy. A vaccine formulation based on an N-terminal fragment of Trans-sialidase (TS) and Immunostimulant Particle Adjuvant (ISPA) - TSNt-ISPA was obtained. Firstly, the immunogenicity and protective capacity of TSNt-ISPA was demonstrated as a prophylactic formulation in an acute model of infection. Later, the formulation was assessed as a therapeutic vaccine alone or combined with (Bz) using two models of chronic infection. BALB/c mice chronically infected with Sylvio X10/4 or Tulahuen cl2 T. cruzi strains were not treated as control or treated only with the therapeutic vaccine TSNt-ISPA, with a combined treatment TSNt-ISPA+Bz (Bz applied after the vaccine), or only with Bz. The vaccination schedule consisted of TSNt-ISPA administration at days110, 120, and 130 post-infection (pi) and Bz administration was performed daily from day 140 to 170 pi. At day 273 pi, electrocardiographic (ECG) parameters, heart parasite load, myocarditis, and heart fibrosis were assessed. In both models, therapeutic administration of TSNt-ISPA reduced ECG alterations and the cardiac tissue damage observed in the chronic phase. Moreover, vaccine treatment significantly decreased heart parasite load in both Sylvio X10/4 and Tulahuen cl2 infected mice. The combined treatment, but not Bz or vaccine administration alone, allowed to restore ECG parameters in Tulahuen cl2 infected mice. The results indicate the usefulness of the therapeutic TSNt-ISPA formulation in BALB/c mice chronically infected with Sylvio X10/4 or Tulahuen cl2 strain. For the mice infected with T. cruzi Tulahuen cl2 strain, the combined treatment with the vaccine and Bz had a more positive effect on the course of heart disease than the individual treatments with the vaccine or Bz alone.

Preclinical Studies and Drug Combination of Low-Cost Molecules for Chagas Disease.

Chagas disease is caused by the protozoan Trypanosoma cruzi (T. cruzi). It remains the major parasitic disease in Latin America and is spreading worldwide, affecting over 10 million people. Hundreds of new compounds with trypanosomicidal action have been identified from different sources such as synthetic or natural molecules, but they have been deficient in several stages of drug development (toxicology, scaling-up, and pharmacokinetics). Previously, we described a series of compounds with simple structures, low cost, and environmentally friendly production with potent trypanosomicidal activity in vitro and in vivo. These molecules are from three different families: thiazolidenehydrazines, diarylideneketones, and steroids. From this collection, we explored their capacity to inhibit the triosephosphate isomerase and cruzipain of T. cruzi. Then, the mechanism of action was explored using NMR metabolomics and computational molecular dynamics. Moreover, the mechanism of death was studied by flow cytometry. Consequently, five compounds, 314, 793, 1018, 1019, and 1260, were pre-clinically studied and their pharmacologic profiles indicated low unspecific toxicity. Interestingly, synergetic effects of diarylideneketones 793 plus 1018 and 793 plus 1019 were evidenced in vitro and in vivo. In vivo, the combination of compounds 793 plus 1018 induced a reduction of more than 90% of the peak of parasitemia in the acute murine model of Chagas disease.

Avaliação do conhecimento sobre a doença de Chagas em escolares das zonas rural e urbana de municípios endêmicos em Minas Gerais / Assessment of knowledge about Chagas disease in schoolchildren in rural and urban areas of endemic municipalities in Minas Gerais state, Brazil

Resumo O objetivo deste estudo foi avaliar o conhecimento de escolares do ensino médio de três escolas localizadas em municípios mineiros endêmicos para a doença de Chagas e extrair informações relativas à sua percepção em relação aos aspectos gerais, biológicos, clínicos e epidemiológicos da doença, do vetor e controle entomológico da doença de Chagas, além de comparar o conhecimento dos participantes em função da localização das escolas (zona rural ou urbana). Para isso, aplicou-se um questionário semiestruturado a 68 alunos. Todos os participantes já ouviram falar a respeito da doença de Chagas, afirmando ter adquirido esse conhecimento, sobretudo, com familiares e escola. Além disso, muitos participantes demonstraram conhecer os hábitos dos vetores, tais como hematofagia e fontes alimentares. Não houve associação clara entre o perfil de urbanização e o conhecimento dos participantes. No entanto, alunos da zona urbana apresentaram menos conhecimento prático a respeito dos triatomíneos e aspectos relativos à transmissão da doença, em relação aos alunos da zona mais "ruralizada". Sugere-se o aprofundamento do tema nos currículos escolares do ensino médio e a necessidade de elaboração de ações de educação em saúde voltadas à vigilância entomológica da doença de Chagas nesses municípios e, provavelmente, em outras regiões do Brasil.

Abstract This study aimed to evaluate the knowledge of high school students from three schools located in endemic municipalities of Minas Gerais to Chagas disease and to extract information related to their perception regarding the general, biological, clinical and epidemiological aspects of the disease, vector and entomological control of Chagas disease, in addition to comparing the knowledge of participants according to the location of schools (rural or urban area). For this, a semi-structured questionnaire was applied to 68 students. All participants have heard about Chagas disease, stating that they have acquired this knowledge, especially with family members and school. In addition, many participants demonstrated to know the habits of vectors, such as hematophagy and dietary sources. There was no clear association between the urbanization profile and the participants' knowledge. However, students from the urban area presented less practical knowledge about triatoins and aspects related to the transmission of the disease, in relation to students in the most "ruralized" area. It is suggested the deepening of the theme in high school curricula and the need to develop health education actions aimed at entomological surveillance of Chagas disease in these municipalities and, probably, in other Brazilian regions.