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Ferpozzi H. Public-Private Partnerships and the Landscape of Neglected Tropical Disease Research: The Shifting Logic and Spaces of Knowledge Production. MINERVA 2023:1-23. [PMID: 37359299 PMCID: PMC10234793 DOI: 10.1007/s11024-023-09496-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/05/2023] [Indexed: 06/28/2023]
Abstract
Until the recent spread of public-private partnerships, pharmaceutical firms had avoided research and development into neglected tropical diseases (NTDs). Because these are diseases that affect the poorest populations in developing regions, research and development initiatives have for the most part depended on the resources and expertise drawn from academia, international organizations, and intermittent state interventions in disease-endemic countries. Over the last few decades, however, public-private product development partnerships (PDPs) have been introducing new collaborative agreements in which the existing resources and expertise combine with the those traditionally withheld by the pharmaceutical industry and global health NGOs. This paper explores recent transformations in the representation of NTDs by examining the shifting logic and spaces of knowledge production which the advent of PDPs has enabled. An analysis of two case studies focused on Chagas disease-related initiatives addresses recurring preoccupations in Science, Technology and Society studies as well as in critical analyses of PDPs: that is, the back-and-forth movement of the disease from being an object of scientific inquiry to a public health concern, and the legitimacy risks and material asymmetries entailed in global health PDPs. Both cases show that it is major global health stakeholders and experts in non-endemic countries, rather than transnational pharmaceutical firms, that exert the greatest influence upon these changing representations: PDPs attempt to expand the preexisting biomedical focus on NTDs by means of incorporating "real world" drug development preoccupations (which I term epistemic shifts), but they also combine their stated global humanitarian aim with security concerns about the diseases spreading to non-endemic, industrialized countries (which I term geographical shifts).
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Affiliation(s)
- Hugo Ferpozzi
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
- Centro de Ciencia, Tecnología y Sociedad, Universidad Maimónides, Buenos Aires, Argentina
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2
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Altcheh J, Moscatelli G, Caruso M, Moroni S, Bisio M, Miranda MR, Monla C, Vaina M, Valdez M, Moran L, Ramirez T, Patiño OL, Riarte A, Gonzalez N, Fernandes J, Alves F, Ribeiro I, Garcia-Bournissen F. Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation. PLoS Negl Trop Dis 2023; 17:e0010850. [PMID: 37256863 DOI: 10.1371/journal.pntd.0010850] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 03/23/2023] [Indexed: 06/02/2023] Open
Abstract
BACKGROUND There is a major need for information on pharmacokinetics (PK) of benznidazole (BNZ) in children with Chagas disease (CD). We conducted a multicentre population PK, safety and efficacy study in children, infants and neonates with CD treated with BNZ (formulated in 100 mg tablets or 12.5 mg dispersible tablets, developed by the pharmaceutical company LAFEPE, in a collaboration with DNDi). METHODS 81 children 0-12 years old were enrolled at 5 pediatric centers in Argentina. Diagnosis of T. cruzi infection was confirmed by direct microscopic examination, or at least two positive conventional serological tests. Subject enrolment was stratified by age: newborns to 2 years (minimum of 10 newborns) and >2-12 years. BNZ 7.5 mg/kg/d was administered in two daily doses for 60 days. Five blood samples per child were obtained at random times within pre-defined time windows at Day 0 at 2-5 h post-dose; during steady state, one sample at Day 7 and at Day 30; and two samples at 12-24 h after final BNZ dose at Day 60. The primary efficacy endpoint was parasitological clearance by qualitative PCR at the end of treatment. RESULTS Forty-one (51%) patients were under 2 years of age (including 14 newborns <1 month of age). Median age at enrolment was 22 months (mean: 43.2; interquartile range (IQR) 7-72 months). The median measured BNZ Cmax was 8.32 mg/L (IQR 5.95-11.8; range 1.79-19.38). Median observed BNZ Cmin (trough) concentration was 2 mg/L (IQR 1.25-3.77; range 0.14-7.08). Overall median simulated Css was 6.3 mg/L (IQR 4.7-8.5 mg/L). CL/F increased quickly during the first month of postnatal life and reached adult levels after approximately 10 years of age. Negative qPCR was observed at the end of treatment in all 76 patients who completed the treatment. Five patients discontinued treatment (3 due to AEs and 2 due to lack of compliance). CONCLUSION We observed lower BNZ plasma concentrations in infants and children than those previously reported in adults treated with comparable mg/kg doses. Despite these lower concentrations, pediatric treatment was well tolerated and universally effective, with a high response rate and infrequent, mild AEs. TRIAL REGISTRATION Registered in clinicaltrials.gov #NCT01549236.
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Affiliation(s)
- Jaime Altcheh
- Servicio de Parasitologia y Chagas, Hospital de Niños "Dr Ricardo Gutierrez", Buenos Aires, Argentina
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Instituto de Investigaciones en Patologias Pediatricas (IMIPP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Guillermo Moscatelli
- Servicio de Parasitologia y Chagas, Hospital de Niños "Dr Ricardo Gutierrez", Buenos Aires, Argentina
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Instituto de Investigaciones en Patologias Pediatricas (IMIPP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Martin Caruso
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Hospital de Niños Doctor Hector Quintana, Jujuy, Argentina
| | - Samanta Moroni
- Servicio de Parasitologia y Chagas, Hospital de Niños "Dr Ricardo Gutierrez", Buenos Aires, Argentina
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Instituto de Investigaciones en Patologias Pediatricas (IMIPP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Margarita Bisio
- Servicio de Parasitologia y Chagas, Hospital de Niños "Dr Ricardo Gutierrez", Buenos Aires, Argentina
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Instituto de Investigaciones en Patologias Pediatricas (IMIPP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Maria Rosa Miranda
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Hospital de Niños Doctor Hector Quintana, Jujuy, Argentina
| | - Celia Monla
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Hospital Público Materno Infantil, Salta, Argentina
| | - Maria Vaina
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Hospital Público Materno Infantil, Salta, Argentina
| | - Maria Valdez
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Hospital Público Materno Infantil, Salta, Argentina
| | - Lucrecia Moran
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Centro de Chagas y Patología Regional, Santiago del Estero, Argentina
| | - Teresa Ramirez
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
| | - Oscar Ledesma Patiño
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Centro de Chagas y Patología Regional, Santiago del Estero, Argentina
| | - Adelina Riarte
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, Buenos Aires, Argentina
| | - Nicolas Gonzalez
- Servicio de Parasitologia y Chagas, Hospital de Niños "Dr Ricardo Gutierrez", Buenos Aires, Argentina
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Instituto de Investigaciones en Patologias Pediatricas (IMIPP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Jayme Fernandes
- Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil
| | - Fabiana Alves
- Drugs for Neglected Diseases initiative, Geneva, Switzerland
| | - Isabela Ribeiro
- Drugs for Neglected Diseases initiative, Geneva, Switzerland
| | - Facundo Garcia-Bournissen
- Servicio de Parasitologia y Chagas, Hospital de Niños "Dr Ricardo Gutierrez", Buenos Aires, Argentina
- PEDCHAGAS Network (Hospital de Niños Ricardo Gutiérrez, Hospital de Niños Doctor Hector Quintana, Hospital Público Materno Infantil, Centro de Chagas y Patología Regional de Santiago del Estero, & Instituto Nacional de Parasitología Dr. Mario Fatala Chaben), Argentina
- Division of Paediatric Clinical Pharmacology, Department of Paediatrics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada
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Rayford KJ, Cooley A, Strode AW, Osi I, Arun A, Lima MF, Misra S, Pratap S, Nde PN. Trypanosoma cruzi dysregulates expression profile of piRNAs in primary human cardiac fibroblasts during early infection phase. Front Cell Infect Microbiol 2023; 13:1083379. [PMID: 36936778 PMCID: PMC10017870 DOI: 10.3389/fcimb.2023.1083379] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 02/13/2023] [Indexed: 03/06/2023] Open
Abstract
Trypanosoma cruzi, the etiological agent of Chagas Disease, causes severe morbidity, mortality, and economic burden worldwide. Though originally endemic to Central and South America, globalization has led to increased parasite presence in most industrialized countries. About 40% of infected individuals will develop cardiovascular, neurological, and/or gastrointestinal pathologies. Accumulating evidence suggests that the parasite induces alterations in host gene expression profiles in order to facilitate infection and pathogenesis. The role of regulatory gene expression machinery during T. cruzi infection, particularly small noncoding RNAs, has yet to be elucidated. In this study, we aim to evaluate dysregulation of a class of sncRNAs called piRNAs during early phase of T. cruzi infection in primary human cardiac fibroblasts by RNA-Seq. We subsequently performed in silico analysis to predict piRNA-mRNA interactions. We validated the expression of these selected piRNAs and their targets during early parasite infection phase by stem loop qPCR and qPCR, respectively. We found about 26,496,863 clean reads (92.72%) which mapped to the human reference genome. During parasite challenge, 441 unique piRNAs were differentially expressed. Of these differentially expressed piRNAs, 29 were known and 412 were novel. In silico analysis showed several of these piRNAs were computationally predicted to target and potentially regulate expression of genes including SMAD2, EGR1, ICAM1, CX3CL1, and CXCR2, which have been implicated in parasite infection, pathogenesis, and various cardiomyopathies. Further evaluation of the function of these individual piRNAs in gene regulation and expression will enhance our understanding of early molecular mechanisms contributing to infection and pathogenesis. Our findings here suggest that piRNAs play important roles in infectious disease pathogenesis and can serve as potential biomarkers and therapeutic targets.
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Affiliation(s)
- Kayla J. Rayford
- Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, United States
| | - Ayorinde Cooley
- Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, United States
| | - Anthony W. Strode
- Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, United States
| | - Inmar Osi
- Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, United States
| | - Ashutosh Arun
- Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, United States
| | - Maria F. Lima
- Biomedical Sciences, School of Medicine, City College of New York, New York, NY, United States
| | - Smita Misra
- School of Graduate Studies and Research, Meharry Medical College, Nashville, TN, United States
| | - Siddharth Pratap
- Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, United States
- Bioinformatics Core, School of Graduate Studies and Research, Meharry Medical College, Nashville, TN, United States
| | - Pius N. Nde
- Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, United States
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4
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Ávila MR, Figueiredo PHS, Lima VP, de Oliveira LFL, de Oliveira LFF, Silva WT, Trede Filho RG, de Carvalho Bastone A, Lacerda ACR, Mendonça VA, Mediano MFF, Costa HS. The prognostic value of the Incremental Shuttle Walk Test in Chagas cardiomyopathy. Disabil Rehabil 2022; 44:7516-7521. [PMID: 34613873 DOI: 10.1080/09638288.2021.1986580] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
PURPOSE To verify the value of the Incremental Shuttle Walk Test (ISWT) distance to identify patients with Chagas cardiomyopathy (ChC) at risk of adverse cardiovascular events. METHODS Fifty-two patients with ChC (51 ± 6 years) were evaluated by ISWT, echocardiography, Cardiopulmonary Exercise Testing, and Human Activity Profile (HAP) Questionnaire. Patients were prospectively followed for 44 ± 10 months. The combined endpoint was cardiac death/heart transplant/stroke. The prognostic value of ISWT was verified by the Cox regression, and the ISWT was adjusted for age, sex, left ventricular ejection fraction (LVEF), and minute ventilation/carbon dioxide production relationship (VE/VCO2 slope). RESULTS At the final follow-up, 11 patients (21%) had experienced the endpoint event. When adjusted for age, sex, LVEF, and VE/VCO2 slope, only ISWT distance (HR 0.99, 95% confidence interval (CI): 0.98-0.99; p = 0.026) and VE/VCO2 slope (HR 0.93, 95% CI: 0.87-0.99; p = 0.044) remained as independent predictors of adverse cardiovascular events in patients with ChC. The optimal cutoff point for identifying poor prognosis was the ISWT distance less than 440 m (AUC = 0.72). There was a significant difference (p = 0.032) in the number of events between the groups with low ISWT distance (≤440 m) and high (>440 m) ISWT distance. CONCLUSIONS The ISWT is a valuable tool with potential value in the prognostic evaluation of patients with ChC.Implications for rehabilitationPatients with Chagas cardiomyopathy showed functional impairment since the early stages of heart disease.The Incremental Shuttle Walk Test (ISWT) can be a valuable and inexpensive tool in the risk stratification of the patients.The ISWT distance is an independent predictor of adverse cardiovascular event.The ISWT distance of 440m is the optimal cut-off point in the identification of patients at risk for adverse cardiovascular events.
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Affiliation(s)
- Matheus Ribeiro Ávila
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Pedro Henrique Scheidt Figueiredo
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil.,Postgraduate Course of Reabilitação e Desempenho Funcional, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Vanessa Pereira Lima
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil.,Postgraduate Course of Reabilitação e Desempenho Funcional, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Luciano Fonseca Lemos de Oliveira
- Department of Physiotherapy, School of Physical Education, Physiotherapy and Occupational Therapy, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Lucas Frois Fernandes de Oliveira
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Whesley Tanor Silva
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Renato Guilherme Trede Filho
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil.,Postgraduate Course of Reabilitação e Desempenho Funcional, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Alessandra de Carvalho Bastone
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil.,Postgraduate Course of Reabilitação e Desempenho Funcional, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Ana Cristina Rodrigues Lacerda
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil.,Postgraduate Course of Reabilitação e Desempenho Funcional, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Vanessa Amaral Mendonça
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil.,Postgraduate Course of Reabilitação e Desempenho Funcional, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | | | - Henrique Silveira Costa
- Physical Therapy School, Healthy and Biological Sciences Faculty, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil.,Postgraduate Course of Reabilitação e Desempenho Funcional, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
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5
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De Salazar PM, Sosa-Estani S, Salvador F, Sulleiro E, Sánchez-Montalvá A, Ribeiro I, Molina I, Buckee CO. Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease. PLoS Negl Trop Dis 2022; 16:e0010828. [PMID: 36409773 PMCID: PMC9721471 DOI: 10.1371/journal.pntd.0010828] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/05/2022] [Accepted: 09/19/2022] [Indexed: 11/22/2022] Open
Abstract
Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of therapeutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accuracy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre- and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilistically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease. Trial Registration: original trial registered with ClinicalTrials.gov, number NCT01489228.
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Affiliation(s)
- Pablo M. De Salazar
- Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
- * E-mail:
| | - Sergio Sosa-Estani
- Drugs for Neglected Diseases Initiative. Rio de Janeiro, Brazil
- Epidemiology and Public Health Research Centre, CONICET, Buenos Aires, Argentina
| | - Fernando Salvador
- Department of Infectious Diseases, Vall d’Hebron University Hospital, International Health Program of the Catalan Institute of Health (PROSICS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Elena Sulleiro
- Department of Microbiology, Vall d’Hebron University Hospital, International Health Program of the Catalan Institute of Health (PROSICS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Adrián Sánchez-Montalvá
- Department of Infectious Diseases, Vall d’Hebron University Hospital, International Health Program of the Catalan Institute of Health (PROSICS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Isabela Ribeiro
- Drugs for Neglected Diseases Initiative, Geneve, Switzerland
| | - Israel Molina
- Department of Infectious Diseases, Vall d’Hebron University Hospital, International Health Program of the Catalan Institute of Health (PROSICS), Barcelona, Spain
- Instituto René Rachou-FIOCRUZ Minas, Laboratório de Triatomíneos e Epidemiologia da Doença de Chagas, Belo Horizonte, Brazil
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Caroline O. Buckee
- Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
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6
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Candia-Puma MA, Machaca-Luque LY, Roque-Pumahuanca BM, Galdino AS, Giunchetti RC, Coelho EAF, Chávez-Fumagalli MA. Accuracy of Diagnostic Tests for the Detection of Chagas Disease: A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2022; 12:2752. [PMID: 36359595 PMCID: PMC9689806 DOI: 10.3390/diagnostics12112752] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/03/2022] [Accepted: 11/04/2022] [Indexed: 11/02/2023] Open
Abstract
The present systematic review and meta-analysis about the accuracy of diagnostic tests aim to describe the findings of literature over the last thirty years for the diagnosis of Chagas disease (CD). This work aimed to determine the accuracy of diagnostic techniques for CD in the disease's acute and chronic phases. The PubMed database was searched for studies published between 1990 and 2021 on CD diagnostics. Fifty-six published studies that met the criteria were analyzed and included in the meta-analysis, evaluating diagnostic accuracy through sensitivity and specificity. For Enzyme-Linked Immunosorbent Assay (ELISA), Fluorescent Antibody Technique (IFAT), Hemagglutination Test (HmT), Polymerase Chain Reaction (PCR), and Real-Time Polymerase Chain Reaction (qPCR) diagnosis methods, the sensitivity had a median of 99.0%, 78.0%, 75.0%, 76.0%, and 94.0%, respectively; while specificity presented a median of 99.0%, 99.0%, 99.0%, 98.0%, and 98.0%, respectively. This meta-analysis showed that ELISA and qPCR techniques had a higher performance compared to other methods of diagnosing CD in the chronic and acute phases, respectively. It was concluded utilizing the Area Under the Curve restricted to the false positive rates (AUCFPR), that the ELISA diagnostic test presents the highest performance in diagnosing acute and chronic CD, compared to serological and molecular tests. Future studies focusing on new CD diagnostics approaches should be targeted.
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Affiliation(s)
- Mayron Antonio Candia-Puma
- Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04000, Peru
- Facultad de Ciencias Farmacéuticas, Bioquímicas y Biotecnológicas, Universidad Católica de Santa María, Arequipa 04000, Peru
| | - Laura Yesenia Machaca-Luque
- Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04000, Peru
- Facultad de Ciencias Farmacéuticas, Bioquímicas y Biotecnológicas, Universidad Católica de Santa María, Arequipa 04000, Peru
| | - Brychs Milagros Roque-Pumahuanca
- Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04000, Peru
- Facultad de Ciencias Farmacéuticas, Bioquímicas y Biotecnológicas, Universidad Católica de Santa María, Arequipa 04000, Peru
| | - Alexsandro Sobreira Galdino
- Laboratório de Biotecnologia de Microrganismos, Universidade Federal São João Del-Rei, Divinópolis 35501-296, MG, Brazil
| | - Rodolfo Cordeiro Giunchetti
- Laboratório de Biologia das Interações Celulares, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
- Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, INCT-DT, Salvador 40015-970, BA, Brazil
| | - Eduardo Antonio Ferraz Coelho
- Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
- Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
| | - Miguel Angel Chávez-Fumagalli
- Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04000, Peru
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Jameson SB, Cloherty E, Londono-Renteria B, Wesson DM. Chagas Disease in the Southeastern USA. CURRENT TROPICAL MEDICINE REPORTS 2022. [DOI: 10.1007/s40475-022-00260-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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8
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Saraiva RM, Mediano MFF, Quintana MS, Sperandio da Silva GM, Costa AR, Sousa AS, Sangenis LHC, Mendes FS, Veloso HH, Xavier SS, Holanda MT, Hasslocher-Moreno AM. Two-dimensional strain derived parameters provide independent predictors of progression to Chagas cardiomyopathy and mortality in patients with Chagas disease. IJC HEART & VASCULATURE 2022; 38:100955. [PMID: 35169612 PMCID: PMC8826593 DOI: 10.1016/j.ijcha.2022.100955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 01/03/2022] [Indexed: 11/24/2022]
Abstract
Background Patients with chronic Chagas disease (CD) cardiomyopathy have a high mortality. We evaluated if two-dimensional (2D) strain (ε) parameters provide independent predictors of progression to CD cardiomyopathy and all-cause mortality. Methods A total of 408 patients with chronic CD (58.6% women; 53 ± 11 years; clinical forms: indeterminate 34.1%, cardiac 57.6%, digestive 1.2%, cardiodigestive 7.1%) were consecutively included in this single-center prospective longitudinal study. Echocardiographic evaluation included left atrial and left ventricular (LV) function on ε analyses. Primary end-point was a composite of all-cause mortality or heart transplant. Secondary end-point was CD progression defined as the occurrence of changes typical of CD in electrocardiogram, sustained ventricular tachycardia, wall motion abnormalities, or heart failure among patients with the indeterminate form at baseline. Multivariable Cox-proportional-hazards regression analyses were performed to test if 2D ε parameters were associated with the studied end-points. P values < 0.05 were considered significant. Results The primary end-point occurred in 91 patients after a follow-up of 6.5 ± 2.7 years. CD progression occurred in 26 out of 144 patients without cardiac form at baseline (2.88 cases/100 patient-years). Peak LV circumferential (HR 1.09, 95% CI 1.01–1.18, P = .02) and radial (HR 0.97, 95% CI 0.95–0.99, P = .007) ε, and LV torsion (HR 0.51, 95% CI 0.35–0.74, P = .0004) were independent predictors of the primary end-point. Peak LV radial ε (HR 0.96, 95% CI 0.93–0.99, P = .03) was an independent predictor of CD progression. Conclusions Therefore, 2D ε derived parameters can be useful for CD progression and mortality prediction.
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Arun A, Rayford KJ, Cooley A, Rana T, Rachakonda G, Villalta F, Pratap S, Lima MF, Sheibani N, Nde PN. Thrombospondin-1 expression and modulation of Wnt and hippo signaling pathways during the early phase of Trypanosoma cruzi infection of heart endothelial cells. PLoS Negl Trop Dis 2022; 16:e0010074. [PMID: 34986160 PMCID: PMC8730400 DOI: 10.1371/journal.pntd.0010074] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 12/08/2021] [Indexed: 12/13/2022] Open
Abstract
The protozoan parasite, Trypanosoma cruzi, causes severe morbidity and mortality in afflicted individuals. Approximately 30% of T. cruzi infected individuals present with cardiac pathology. The invasive forms of the parasite are carried in the vascular system to infect other cells of the body. During transportation, the molecular mechanisms by which the parasite signals and interact with host endothelial cells (EC) especially heart endothelium is currently unknown. The parasite increases host thrombospondin-1 (TSP1) expression and activates the Wnt/β-catenin and hippo signaling pathways during the early phase of infection. The links between TSP1 and activation of the signaling pathways and their impact on parasite infectivity during the early phase of infection remain unknown. To elucidate the significance of TSP1 function in YAP/β-catenin colocalization and how they impact parasite infectivity during the early phase of infection, we challenged mouse heart endothelial cells (MHEC) from wild type (WT) and TSP1 knockout mice with T. cruzi and evaluated Wnt signaling, YAP/β-catenin crosstalk, and how they affect parasite infection. We found that in the absence of TSP1, the parasite induced the expression of Wnt-5a to a maximum at 2 h (1.73±0.13), P< 0.001 and enhanced the level of phosphorylated glycogen synthase kinase 3β at the same time point (2.99±0.24), P<0.001. In WT MHEC, the levels of Wnt-5a were toned down and the level of p-GSK-3β was lowest at 2 h (0.47±0.06), P< 0.01 compared to uninfected control. This was accompanied by a continuous significant increase in the nuclear colocalization of β-catenin/YAP in TSP1 KO MHEC with a maximum Pearson correlation coefficient of (0.67±0.02), P< 0.05 at 6 h. In WT MHEC, the nuclear colocalization of β-catenin/YAP remained steady and showed a reduction at 6 h (0.29±0.007), P< 0.05. These results indicate that TSP1 plays an important role in regulating β-catenin/YAP colocalization during the early phase of T. cruzi infection. Importantly, dysregulation of this crosstalk by pre-incubation of WT MHEC with a β-catenin inhibitor, endo-IWR 1, dramatically reduced the level of infection of WT MHEC. Parasite infectivity of inhibitor treated WT MHEC was similar to the level of infection of TSP1 KO MHEC. These results indicate that the β-catenin pathway induced by the parasite and regulated by TSP1 during the early phase of T. cruzi infection is an important potential therapeutic target, which can be explored for the prophylactic prevention of T. cruzi infection.
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Affiliation(s)
- Ashutosh Arun
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, United States of America
| | - Kayla J. Rayford
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, United States of America
| | - Ayorinde Cooley
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, United States of America
| | - Tanu Rana
- Department of Professional Medical Education and Molecular Biology Core Facility, Meharry Medical College, Nashville, Tennessee, United States of America
| | - Girish Rachakonda
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, United States of America
| | - Fernando Villalta
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, United States of America
| | - Siddharth Pratap
- School of Graduate Studies and Research, Meharry Medical College, Nashville, Tennessee, United States of America
| | - Maria F. Lima
- School of Graduate Studies and Research, Meharry Medical College, Nashville, Tennessee, United States of America
- Department of Molecular and Cellular and Biomedical Sciences, School of Medicine, The City College of New York, New York, United States of America
| | - Nader Sheibani
- Department of Ophthalmology and Visual Sciences, Biomedical Engineering, and Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America
| | - Pius N. Nde
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, United States of America
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Saraiva RM, Mediano MFF, Mendes FSNS, Sperandio da Silva GM, Veloso HH, Sangenis LHC, Silva PSD, Mazzoli-Rocha F, Sousa AS, Holanda MT, Hasslocher-Moreno AM. Chagas heart disease: An overview of diagnosis, manifestations, treatment, and care. World J Cardiol 2021; 13:654-675. [PMID: 35070110 PMCID: PMC8716970 DOI: 10.4330/wjc.v13.i12.654] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/11/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
Chagas heart disease (CHD) affects approximately 30% of patients chronically infected with the protozoa Trypanosoma cruzi. CHD is classified into four stages of increasing severity according to electrocardiographic, echocardiographic, and clinical criteria. CHD presents with a myriad of clinical manifestations, but its main complications are sudden cardiac death, heart failure, and stroke. Importantly, CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies, and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies. Among patients with CHD, approximately 90% of deaths can be attributed to complications of Chagas disease. Sudden cardiac death is the most common cause of death (55%–60%), followed by heart failure (25%–30%) and stroke (10%–15%). The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with. Therefore, the management of CHD is challenging, and in this review, we present the most updated available data to help clinicians and cardiologists in the care of these patients. We describe the clinical manifestations, diagnosis and classification criteria, risk stratification, and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.
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Affiliation(s)
- Roberto M Saraiva
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Mauro Felippe F Mediano
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Fernanda SNS Mendes
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | | | - Henrique H Veloso
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Luiz Henrique C Sangenis
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Paula Simplício da Silva
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Flavia Mazzoli-Rocha
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Andréa S Sousa
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Marcelo T Holanda
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Alejandro M Hasslocher-Moreno
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
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Busselman RE, Hamer SA. Chagas Disease Ecology in the United States: Recent Advances in Understanding Trypanosoma cruzi Transmission Among Triatomines, Wildlife, and Domestic Animals and a Quantitative Synthesis of Vector-Host Interactions. Annu Rev Anim Biosci 2021; 10:325-348. [PMID: 34758274 DOI: 10.1146/annurev-animal-013120-043949] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Chagas disease, a neglected tropical disease present in the Americas, is caused by the parasite Trypanosoma cruzi and is transmitted by triatomine kissing bug vectors. Hundreds of vertebrate host species are involved in the ecology of Chagas disease. The sylvatic nature of most triatomines found in the United States accounts for high levels of animal infections but few reports of human infections. This review focuses on triatomine distributions and animal infections in the southern United States. A quantitative synthesis of available US data from triatomine bloodmeal analysis studies shows that dogs, humans, and rodents are key taxa for feeding triatomines. Imperfect and unvalidated diagnostic tools in wildlife complicate the study of animal T. cruzi infections, and integrated vector management approaches are needed to reduce parasite transmission in nature. The diversity of animal species involved in Chagas disease ecology underscores the importance of a One Health approach for disease research and management. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Rachel E Busselman
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA;
| | - Sarah A Hamer
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA;
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Diversity of Trypanosoma cruzi parasites infecting Triatoma dimidiata in Central Veracruz, Mexico, and their One Health ecological interactions. INFECTION GENETICS AND EVOLUTION 2021; 95:105050. [PMID: 34450293 DOI: 10.1016/j.meegid.2021.105050] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/17/2021] [Accepted: 08/21/2021] [Indexed: 01/21/2023]
Abstract
Triatoma dimidiata is the main vector of Trypanosoma cruzi parasites in Veracruz, Mexico, and its association with human housing appears variable. Also, in spite of a high seroprevalence of T. cruzi infection in humans, parasite transmission remains poorly understood. Therefore, we aimed to identify T. dimidiata blood feeding sources and its parasite and microbial diversity to reconstruct T. cruzi parasite transmission ecology in central Veracruz, Mexico, within a One Health/Ecohealth framework. We used a metabarcoding and deep sequencing approach of specific markers for the simultaneous identification of T. dimidiata haplogroup (ITS-2), vertebrate blood meals (12 s gene), T. cruzi parasites (mini-exon gene), and gut microbiota (bacterial 16 s). Twelve species of domestic/synanthropic animals and humans were identified as blood sources, with multiple feeding on 4.2 ± 0.4 hosts per bug. The feeding/parasite transmission network was strongly centered on humans, emphasizing a significant risk of infection. We also unambiguously confirmed the presence of TcI, TcII, TcV and TcVI DTUs in T. dimidiata, and sequences from Veracruz tended to cluster apart from parasites from other regions, suggesting some level of local differentiation. Analysis of T. dimidiata microbiota suggested that several bacterial families may be associated with the presence/absence of T. cruzi, and some of these associations may also be parasite DTU-specific. Such integrative approaches within the EcoHealth/One Health framework provide key insights on T. cruzi transmission and potential novel strategies for disease control.
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13
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Polonio R, López-Domínguez J, Herrera C, Dumonteil E. Molecular ecology of Triatoma dimidiata in southern Belize reveals risk for human infection and the local differentiation of Trypanosoma cruzi parasites. Int J Infect Dis 2021; 108:320-329. [PMID: 34098097 DOI: 10.1016/j.ijid.2021.05.083] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/21/2021] [Accepted: 05/31/2021] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE In Belize, the main vector for Trypanosoma cruzi, the agent of Chagas disease, is Triatoma dimidiata, but transmission cycles and the risk for human infection are unclear. Therefore, the aim of this study was to identify T. dimidiata blood feeding sources and its parasite and microbial diversity, in order to reconstruct T. cruzi parasite transmission ecology in southern Belize. METHODS A metabarcoding approach based on deep sequencing of markers was used for bug taxonomy, blood meal sources, T. cruzi genotypes, and microbiota composition. Bugs were collected in 13 villages of Toledo district. RESULTS Bugs fed on at least 13 species, from domestic hosts such as humans, dogs, cows, and pigs, to synanthropic species such as mice, rats, and opossums, and sylvatic species such as deer, peccary, and kinkajou, in agreement with an opportunistic feeding behavior. Nonetheless, most feeding focused on a few species, including humans. Infection with T. cruzi was detected in 24 of 39 bugs (62%), and the analysis of 242 T. cruzi mini-exon sequences (average 10 ± 5 haplotypes per bug) indicated the presence of TcI and TcIV parasite discrete typing units (DTUs). However, for both DTUs, sequences from Belize mostly clustered apart from sequences from North and South America, suggesting the local differentiation of parasites. T. dimidiata also harbored a diverse bacterial microbiota, with ontogenic changes suggesting microbiota maturation during nymphal development. CONCLUSIONS Together, these results indicate a significant risk for T. cruzi infection in humans. They also highlight the need to better characterize the diversity of T. cruzi strains in the region and its impact on disease epidemiology.
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Affiliation(s)
- Roy Polonio
- University of Belize, Punta Gorda, Toledo, Belize
| | - Jaime López-Domínguez
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA; LADISER Inmunología y Biología Molecular, Facultad de Ciencias Químicas, Universidad Veracruzana, Orizaba, Veracruz, Mexico; Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Veracruz, Mexico
| | - Claudia Herrera
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA
| | - Eric Dumonteil
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA.
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14
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Diversity and interactions among triatomine bugs, their blood feeding sources, gut microbiota and Trypanosoma cruzi in the Sierra Nevada de Santa Marta in Colombia. Sci Rep 2021; 11:12306. [PMID: 34112903 PMCID: PMC8192545 DOI: 10.1038/s41598-021-91783-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/25/2021] [Indexed: 12/14/2022] Open
Abstract
Chagas disease remains a major neglected disease in Colombia. We aimed to characterize Trypanosoma cruzi transmission networks in the Sierra Nevada de Santa Marta (SNSM) region, to shed light on disease ecology and help optimize control strategies. Triatomines were collected in rural communities and analyzed for blood feeding sources, parasite diversity and gut microbiota composition through a metagenomic and deep sequencing approach. Triatoma dimidiata predominated, followed by Rhodnius prolixus, Triatoma maculata, Rhodnius pallescens, Panstrongylus geniculatus and Eratyrus cuspidatus. Twenty-two species were identified as blood sources, resulting in an integrated transmission network with extensive connectivity among sylvatic and domestic host species. Only TcI parasites were detected, predominantly from TcIb but TcIa was also reported. The close relatedness of T. cruzi strains further supported the lack of separate transmission cycles according to habitats or triatomine species. Triatomine microbiota varied according to species, developmental stage and T. cruzi infection. Bacterial families correlated with the presence/absence of T. cruzi were identified. In conclusion, we identified a domestic transmission cycle encompassing multiple vector species and tightly connected with sylvatic hosts in the SNSM region, rather than an isolated domestic transmission cycle. Therefore, integrated interventions targeting all vector species and their contact with humans should be considered.
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15
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Ndayishimiye J, Popat A, Kumeria T, Blaskovich MA, Robert Falconer J. Supercritical carbon dioxide assisted complexation of benznidazole: γ-cyclodextrin for improved dissolution. Int J Pharm 2021; 596:120240. [DOI: 10.1016/j.ijpharm.2021.120240] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/16/2020] [Accepted: 12/17/2020] [Indexed: 12/12/2022]
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Díaz ALM, Pregonero Sigua F, Otálora AS, Pedraza Bernal AM. Trypanosoma cruzi seroprevalence and associated factors in women in Casanare-Colombia. J Parasit Dis 2021; 45:89-95. [PMID: 33746391 PMCID: PMC7921244 DOI: 10.1007/s12639-020-01280-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 09/22/2020] [Indexed: 10/23/2022] Open
Abstract
Chagas disease is caused by the parasite Trypanosoma cruzi and transmitted mainly by triatomines and from mothers to children. In Colombia, this disease is a public health problem and due to its high endemicity and vertical transmission, women are susceptible populations that must be evaluated. Our objective was to determinate the Trypanosoma cruzi seroprevalence and factors associated with women in Pore (Municipality), Casanare, Colombia. Cross-sectional study. A sample of 230 healthy volunteer women, 15 years or older, without previous diagnosis of Chagas disease was taken; the serological analysis was done using the Chagas ELISA IgG and IgM and indirect Hemagglutination (HAI) technique. In addition, a survey was applied to each participant in order to explore the presence of factors that could be associated with a positive test result. The seropostitivity found in Pore Casanare's women was 16.9% (39/230, 95% CI 12.1-21.7), additionally it was found that rural origin, the coexistence with animals, especially chickens, age, low level schooling and housing material are factors associated with T. cruzi infection in this population. The results of this study indicate the importance of conducting extensive seroepidemiological studies in populations of endemic areas, due to the difficulty in detecting cases in the acute phase; therefore, screening allows the establishment of a follow-up and treatment time line that contributes to the interruption of the transmission vertical.
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17
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Zamora LE, Palacio F, Kozlowski DS, Doraivelu K, Dude CM, Jamieson DJ, Haddad LB. Chagas Disease Screening Using Point-of-Care Testing in an At-Risk Obstetric Population. Am J Trop Med Hyg 2020; 104:959-963. [PMID: 33350375 PMCID: PMC7941822 DOI: 10.4269/ajtmh.20-0517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 11/02/2020] [Indexed: 01/03/2023] Open
Abstract
Congenital transmission is the most important mode of transmission of Chagas disease (CD) in non-endemic countries. Identifying CD in reproductive-aged women is essential to reduce the risk of transmitting the disease to their children and offer treatment to women and their children, which could cure the disease. We evaluated the use of point-of-care (POC) testing for CD in postpartum patients. In our patient population, 16.7% (23/138) tested positive by POC testing, but confirmatory testing was negative for all patients. Among those considered high risk, 30% declined participation. Our results suggest limited utility of the point-of-care test used in our study and identify an opportunity for improvement to broaden diagnostic testing options. Our study also highlights the need to develop strategies to increase subject participation in future research.
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Affiliation(s)
- Lindsey E Zamora
- Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Federico Palacio
- Division of Infectious Diseases, Department of Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Debra S Kozlowski
- Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia
| | - Kamini Doraivelu
- Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia
| | - Carolynn M Dude
- Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia
| | - Denise J Jamieson
- Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia
| | - Lisa B Haddad
- Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia
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Trypanosoma cruzi Modulates PIWI-Interacting RNA Expression in Primary Human Cardiac Myocytes during the Early Phase of Infection. Int J Mol Sci 2020; 21:ijms21249439. [PMID: 33322418 PMCID: PMC7764157 DOI: 10.3390/ijms21249439] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 11/28/2020] [Accepted: 12/10/2020] [Indexed: 02/07/2023] Open
Abstract
Trypanosoma cruzi dysregulates the gene expression profile of primary human cardiomyocytes (PHCM) during the early phase of infection through a mechanism which remains to be elucidated. The role that small non-coding RNAs (sncRNA) including PIWI-interacting RNA (piRNA) play in regulating gene expression during the early phase of infection is unknown. To understand how T. cruzi dysregulate gene expression in the heart, we challenged PHCM with T. cruzi trypomastigotes and analyzed sncRNA, especially piRNA, by RNA-sequencing. The parasite induced significant differential expression of host piRNAs, which can target and regulate the genes which are important during the early infection phase. An average of 21,595,866 (88.40%) of clean reads mapped to the human reference genome. The parasite induced 217 unique piRNAs that were significantly differentially expressed (q ≥ 0.8). Of these differentially expressed piRNAs, 6 were known and 211 were novel piRNAs. In silico analysis showed that some of the dysregulated known and novel piRNAs could target and potentially regulate the expression of genes including NFATC2, FOS and TGF-β1, reported to play important roles during T. cruzi infection. Further evaluation of the specific functions of the piRNAs in the regulation of gene expression during the early phase of infection will enhance our understanding of the molecular mechanism of T. cruzi pathogenesis. Our novel findings constitute the first report that T. cruzi can induce differential expression of piRNAs in PHCM, advancing our knowledge about the involvement of piRNAs in an infectious disease model, which can be exploited for biomarker and therapeutic development.
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Dumonteil E, Pronovost H, Bierman EF, Sanford A, Majeau A, Moore R, Herrera C. Interactions among Triatoma sanguisuga blood feeding sources, gut microbiota and Trypanosoma cruzi diversity in southern Louisiana. Mol Ecol 2020; 29:3747-3761. [PMID: 32749727 DOI: 10.1111/mec.15582] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 07/20/2020] [Accepted: 07/27/2020] [Indexed: 12/15/2022]
Abstract
Integrating how biodiversity and infectious disease dynamics are linked at multiple levels and scales is highly challenging. Chagas disease is a vector-borne disease, with specificities of the triatomine vectors and Trypanosoma cruzi parasite life histories resulting in a complex multihost and multistrain life cycle. Here, we tested the hypothesis that T. cruzi transmission cycles are shaped by triatomine host communities and gut microbiota composition by comparing the integrated interactions of Triatoma sanguisuga in southern Louisiana with feeding hosts, T. cruzi parasite and bacterial microbiota in two habitats. Bugs were collected from resident's houses and animal shelters and analysed for genetic structure, blood feeding sources, T. cruzi parasites, and bacterial diversity by PCR amplification of specific DNA markers followed by next-generation sequencing, in an integrative metabarcoding approach. T. sanguisuga feeding host communities appeared opportunistic and defined by host abundance in each habitat, yielding distinct parasite transmission networks among hosts. The circulation of a large diversity of T. cruzi DTUs was also detected, with TcII and TcV detected for the first time in triatomines in the US. The bacterial microbiota was highly diverse and varied significantly according to the DTU infecting the bugs, indicating specific interactions among them in the gut. Expanding such studies to multiple habitats and additional triatomine species would be key to further refine our understanding of the complex life cycles of multihost, multistrain parasites such as T. cruzi, and may lead to improved disease control strategies.
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Affiliation(s)
- Eric Dumonteil
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA
| | - Henry Pronovost
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA
| | - Eli F Bierman
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA
| | - Anna Sanford
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA
| | - Alicia Majeau
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA
| | - Ryan Moore
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA
| | - Claudia Herrera
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA
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Sijm M, Sterk GJ, Caljon G, Maes L, de Esch IJP, Leurs R. Structure-Activity Relationship of Phenylpyrazolones against Trypanosoma cruzi. ChemMedChem 2020; 15:1310-1321. [PMID: 32249532 PMCID: PMC7496920 DOI: 10.1002/cmdc.202000136] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 03/29/2020] [Indexed: 11/10/2022]
Abstract
Chagas disease is a neglected parasitic disease caused by the parasitic protozoan Trypanosoma cruzi and currently affects around 8 million people. Previously, 2-isopropyl-5-(4-methoxy-3-(pyridin-3-yl)phenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0227) was discovered to be a sub-micromolar inhibitor (pIC50 =6.4) of T. cruzi. So far, SAR investigations of this scaffold have focused on the alkoxy substituent, the pyrazolone nitrogen substituent and the aromatic substituent of the core phenylpyrazolone. In this study, modifications of the phenyldihydropyrazolone scaffold are described. Variations were introduced by installing different substituents on the phenyl core, modifying the geminal dimethyl and installing various bio-isosteres of the dihydropyrazolone group. The anti T. cruzi activity of NPD-0227 could not be surpassed as the most potent compounds show pIC50 values of around 6.3. However, valuable additional SAR data for this interesting scaffold was obtained, and the data suggest that a scaffold hop is feasible as the pyrazolone moiety can be replaced by a oxazole or oxadiazole with minimal loss of activity.
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Affiliation(s)
- Maarten Sijm
- Division of Medicinal Chemistry, Faculty of SciencesAmsterdam Institute for Molecules, Medicines and Systems (AIMMS)Vrije Universiteit AmsterdamDe Boelelaan 11081081 HZAmsterdamThe Netherlands
| | - Geert Jan Sterk
- Division of Medicinal Chemistry, Faculty of SciencesAmsterdam Institute for Molecules, Medicines and Systems (AIMMS)Vrije Universiteit AmsterdamDe Boelelaan 11081081 HZAmsterdamThe Netherlands
| | - Guy Caljon
- Laboratory for Microbiology, Parasitology and Hygiene (LMPH)University of AntwerpUniversiteitsplein 12610AntwerpenBelgium
| | - Louis Maes
- Laboratory for Microbiology, Parasitology and Hygiene (LMPH)University of AntwerpUniversiteitsplein 12610AntwerpenBelgium
| | - Iwan J. P. de Esch
- Division of Medicinal Chemistry, Faculty of SciencesAmsterdam Institute for Molecules, Medicines and Systems (AIMMS)Vrije Universiteit AmsterdamDe Boelelaan 11081081 HZAmsterdamThe Netherlands
| | - Rob Leurs
- Division of Medicinal Chemistry, Faculty of SciencesAmsterdam Institute for Molecules, Medicines and Systems (AIMMS)Vrije Universiteit AmsterdamDe Boelelaan 11081081 HZAmsterdamThe Netherlands
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21
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Arun A, Rayford KJ, Cooley A, Rachakonda G, Villalta F, Pratap S, Lima MF, Sheibani N, Nde PN. Thrombospondin-1 Plays an Essential Role in Yes-Associated Protein Nuclear Translocation during the Early Phase of Trypanosoma cruzi Infection in Heart Endothelial Cells. Int J Mol Sci 2020; 21:ijms21144912. [PMID: 32664627 PMCID: PMC7403984 DOI: 10.3390/ijms21144912] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/09/2020] [Accepted: 07/09/2020] [Indexed: 01/03/2023] Open
Abstract
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease. This neglected tropical disease causes severe morbidity and mortality in endemic regions. About 30% of T. cruzi infected individuals will present with cardiac complications. Invasive trypomastigotes released from infected cells can be carried in the vascular endothelial system to infect neighboring and distant cells. During the process of cellular infection, the parasite induces host cells, to increase the levels of host thrombospondin-1 (TSP-1), to facilitate the process of infection. TSP-1 plays important roles in the functioning of vascular cells, including vascular endothelial cells with important implications in cardiovascular health. Many signal transduction pathways, including the yes-associated protein 1 (YAP)/transcriptional coactivator, with PDZ-binding motif (TAZ) signaling, which are upstream of TSP-1, have been linked to the pathophysiology of heart damage. The molecular mechanisms by which T. cruzi signals, and eventually infects, heart endothelial cells remain unknown. To evaluate the importance of TSP-1 expression in heart endothelial cells during the process of T. cruzi infection, we exposed heart endothelial cells prepared from Wild Type and TSP-1 Knockout mouse to invasive T. cruzi trypomastigotes at multiple time points, and evaluated changes in the hippo signaling cascade using immunoblotting and immunofluorescence assays. We found that the parasite turned off the hippo signaling pathway in TSP-1KO heart endothelial cells. The levels of SAV1 and MOB1A increased to a maximum of 2.70 ± 0.23 and 5.74 ± 1.45-fold at 3 and 6 h, respectively, in TSP-1KO mouse heart endothelial cells (MHEC), compared to WT MHEC, following a parasite challenge. This was accompanied by a significant continuous increase in the nuclear translocation of downstream effector molecule YAP, to a maximum mean nuclear fluorescence intensity of 10.14 ± 0.40 at 6 h, compared to wild type cells. Furthermore, we found that increased nuclear translocated YAP significantly colocalized with the transcription co-activator molecule pan-TEAD, with a maximum Pearson's correlation coefficient of 0.51 ± 0.06 at 6 h, compared to YAP-Pan-TEAD colocalization in the WT MHEC, which decreased significantly, with a minimum Pearson's correlation coefficient of 0.30 ± 0.01 at 6 h. Our data indicate that, during the early phase of infection, upregulated TSP-1 is essential for the regulation of the hippo signaling pathway. These studies advance our understanding of the molecular interactions occurring between heart endothelial cells and T. cruzi, in the presence and absence of TSP-1, providing insights into processes linked to parasite dissemination and pathogenesis.
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Affiliation(s)
- Ashutosh Arun
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, TN 37208, USA; (A.A.); (K.J.R.); (A.C.); (G.R.); (F.V.)
| | - Kayla J. Rayford
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, TN 37208, USA; (A.A.); (K.J.R.); (A.C.); (G.R.); (F.V.)
| | - Ayorinde Cooley
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, TN 37208, USA; (A.A.); (K.J.R.); (A.C.); (G.R.); (F.V.)
| | - Girish Rachakonda
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, TN 37208, USA; (A.A.); (K.J.R.); (A.C.); (G.R.); (F.V.)
| | - Fernando Villalta
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, TN 37208, USA; (A.A.); (K.J.R.); (A.C.); (G.R.); (F.V.)
| | - Siddharth Pratap
- School of Graduate Studies and Research, Meharry Medical College, Nashville, TN 37208, USA; (S.P.); (M.F.L.)
| | - Maria F. Lima
- School of Graduate Studies and Research, Meharry Medical College, Nashville, TN 37208, USA; (S.P.); (M.F.L.)
- Department of Molecular Cellular and Biomedical Sciences, School of Medicine, The City College of New York, New York, NY 10031, USA
| | - Nader Sheibani
- Department of Ophthalmology and Visual Sciences, Biomedical Engineering and Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA;
| | - Pius N. Nde
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, TN 37208, USA; (A.A.); (K.J.R.); (A.C.); (G.R.); (F.V.)
- Correspondence: ; Tel.: +1-615-327-6997
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22
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Alves SMM, Alvarado-Arnês LE, Cavalcanti MDGADM, Carrazzone CDFV, Pacheco AGF, Sarteschi C, Moraes MO, de Oliveira WA, Medeiros CDA, Pessoa FG, Mady C, Lannes-Vieira J, Ramires FJA. Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease. Rev Soc Bras Med Trop 2020; 53:e20190488. [PMID: 32638886 PMCID: PMC7341830 DOI: 10.1590/0037-8682-0488-2019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 05/20/2020] [Indexed: 12/01/2022] Open
Abstract
INTRODUCTION Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy. METHODS We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment. RESULTS A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04). CONCLUSIONS Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.
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Affiliation(s)
- Silvia Marinho Martins Alves
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP,
Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
- Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de
Biologia das Interações, Rio de Janeiro, RJ, Brasil
- Ambulatório de Doença de Chagas e Insuficiência Cardíaca, Pronto
Socorro Cardiológico de Pernambuco (PROCAPE)/UPE, Recife, PE, Brasil
| | - Lúcia Elena Alvarado-Arnês
- Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de
Biologia das Interações, Rio de Janeiro, RJ, Brasil
- Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de
Hanseníase, Rio de Janeiro, RJ, Brasil
| | | | | | | | - Camila Sarteschi
- Realcor - Real Hospital Português de Beneficência, Recife, PE,
Brasil
| | - Milton Ozorio Moraes
- Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de
Hanseníase, Rio de Janeiro, RJ, Brasil
| | - Wilson Alves de Oliveira
- Ambulatório de Doença de Chagas e Insuficiência Cardíaca, Pronto
Socorro Cardiológico de Pernambuco (PROCAPE)/UPE, Recife, PE, Brasil
| | - Carolina de Araújo Medeiros
- Ambulatório de Doença de Chagas e Insuficiência Cardíaca, Pronto
Socorro Cardiológico de Pernambuco (PROCAPE)/UPE, Recife, PE, Brasil
| | - Fernanda Gallinaro Pessoa
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP,
Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
| | - Charles Mady
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP,
Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
| | - Joseli Lannes-Vieira
- Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de
Biologia das Interações, Rio de Janeiro, RJ, Brasil
| | - Felix José Alvarez Ramires
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP,
Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
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23
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Perez-Zetune V, Bialek SR, Montgomery SP, Stillwaggon E. Congenital Chagas Disease in the United States: The Effect of Commercially Priced Benznidazole on Costs and Benefits of Maternal Screening. Am J Trop Med Hyg 2020; 102:1086-1089. [PMID: 32100696 PMCID: PMC7204569 DOI: 10.4269/ajtmh.20-0005] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors, and through transfusions, transplants, insect feces in food, and mother to child during gestation. An estimated 30% of infected persons will develop lifelong, potentially fatal cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment for Chagas disease in the United States, including the cost of commercially available benznidazole. We compare costs of testing and treatment for mothers and infants with the lifetime societal costs without testing and consequent morbidity and mortality due to lack of treatment or late treatment. We constructed a decision-analytic model, using one tree that shows the combined costs for every possible mother–child pairing. Savings per birth in a targeted screening program are $1,314, and with universal screening, $105 per birth. At current screening costs, universal screening results in $420 million in lifetime savings per birth-year cohort. We found that a congenital Chagas screening program in the United States is cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence greater than 0.06% compared with no screening program.
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Affiliation(s)
| | - Stephanie R Bialek
- Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Susan P Montgomery
- Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
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24
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Branco Santos JC, de Melo JA, Maheshwari S, de Medeiros WMTQ, de Freitas Oliveira JW, Moreno CJ, Mario Amzel L, Gabelli SB, Sousa Silva M. Bisphosphonate-Based Molecules as Potential New Antiparasitic Drugs. Molecules 2020; 25:E2602. [PMID: 32503272 PMCID: PMC7321420 DOI: 10.3390/molecules25112602] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 05/20/2020] [Accepted: 05/27/2020] [Indexed: 12/20/2022] Open
Abstract
Neglected tropical diseases such as Chagas disease and leishmaniasis affect millions of people around the world. Both diseases affect various parts of the globe and drugs traditionally used in therapy against these diseases have limitations, especially with regard to low efficacy and high toxicity. In this context, the class of bisphosphonate-based compounds has made significant advances regarding the chemical synthesis process as well as the pharmacological properties attributed to these compounds. Among this spectrum of pharmacological activity, bisphosphonate compounds with antiparasitic activity stand out, especially in the treatment of Chagas disease and leishmaniasis caused by Trypanosoma cruzi and Leishmania spp., respectively. Some bisphosphonate compounds can inhibit the mevalonate pathway, an essential metabolic pathway, by interfering with the synthesis of ergosterol, a sterol responsible for the growth and viability of these parasites. Therefore, this review aims to present the information about the importance of these compounds as antiparasitic agents and as potential new drugs to treat Chagas disease and leishmaniasis.
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Affiliation(s)
- Joice Castelo Branco Santos
- Immunoparasitology Laboratory, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil; (J.C.B.S.); (J.A.d.M.); (W.M.T.Q.d.M.); (J.W.d.F.O.); (C.J.M.)
- Postgraduate Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil
| | - Jonathas Alves de Melo
- Immunoparasitology Laboratory, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil; (J.C.B.S.); (J.A.d.M.); (W.M.T.Q.d.M.); (J.W.d.F.O.); (C.J.M.)
- Postgraduate Program in Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil
| | - Sweta Maheshwari
- Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (S.M.); (L.M.A.)
| | - Wendy Marina Toscano Queiroz de Medeiros
- Immunoparasitology Laboratory, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil; (J.C.B.S.); (J.A.d.M.); (W.M.T.Q.d.M.); (J.W.d.F.O.); (C.J.M.)
- Postgraduate Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil
| | - Johny Wysllas de Freitas Oliveira
- Immunoparasitology Laboratory, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil; (J.C.B.S.); (J.A.d.M.); (W.M.T.Q.d.M.); (J.W.d.F.O.); (C.J.M.)
- Postgraduate Program in Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil
| | - Cláudia Jassica Moreno
- Immunoparasitology Laboratory, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil; (J.C.B.S.); (J.A.d.M.); (W.M.T.Q.d.M.); (J.W.d.F.O.); (C.J.M.)
- Postgraduate Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil
- Postgraduate Program in Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil
| | - L. Mario Amzel
- Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (S.M.); (L.M.A.)
| | - Sandra B. Gabelli
- Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (S.M.); (L.M.A.)
- Department of Medicine and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Marcelo Sousa Silva
- Immunoparasitology Laboratory, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil; (J.C.B.S.); (J.A.d.M.); (W.M.T.Q.d.M.); (J.W.d.F.O.); (C.J.M.)
- Postgraduate Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil
- Postgraduate Program in Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte, 59012-570 Natal, Brazil
- Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, New University of Lisbon, 1800-166 Lisbon, Portugal
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25
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Gottwald T, Luo W, Posny D, Riley T, Louws F. A probabilistic census-travel model to predict introduction sites of exotic plant, animal and human pathogens. Philos Trans R Soc Lond B Biol Sci 2020; 374:20180260. [PMID: 31104596 PMCID: PMC6558561 DOI: 10.1098/rstb.2018.0260] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
International travel offers an extensive network for new and recurring human-mediated introductions of exotic infectious pathogens and biota, freeing geographical constraints. We present a predictive census-travel model that integrates international travel with endpoint census data and epidemiological characteristics to predict points of introduction. Population demographics, inbound and outbound travel patterns, and quantification of source strength by country are combined to estimate and rank risk of introduction at user-scalable land parcel areas (e.g. state, county, zip code, census tract, gridded landscapes (1 mi2, 5 km2, etc.)). This risk ranking by parcel can be used to develop pathogen surveillance programmes, and has been incorporated in multiple US state/federal surveillance protocols. The census-travel model is versatile and independent of pathosystems, and applies a risk algorithm to generate risk maps for plant, human and animal contagions at different spatial scales. An interactive, user-friendly interface is available online (https://epi-models.shinyapps.io/Census_Travel/) to provide ease-of-use for regulatory agencies for early detection of high-risk exotics. The interface allows users to parametrize and run the model without knowledge of background code and underpinning data. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'. This theme issue is linked with the earlier issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'.
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Affiliation(s)
- Tim Gottwald
- 1 US Department of Agriculture, Agricultural Research Service , Fort Pierce, FL 34945 , USA
| | - Weiqi Luo
- 1 US Department of Agriculture, Agricultural Research Service , Fort Pierce, FL 34945 , USA.,2 Center for Integrated Pest Management, North Carolina State University , Raleigh, NC 27695 , USA
| | - Drew Posny
- 1 US Department of Agriculture, Agricultural Research Service , Fort Pierce, FL 34945 , USA.,2 Center for Integrated Pest Management, North Carolina State University , Raleigh, NC 27695 , USA
| | - Tim Riley
- 3 US Department of Agriculture, Animal and Plant Health Inspection Service , Orlando, FL 32824 , USA
| | - Frank Louws
- 2 Center for Integrated Pest Management, North Carolina State University , Raleigh, NC 27695 , USA
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26
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Kendricks AL, Gray SB, Wilkerson GK, Sands CM, Abee CR, Bernacky BJ, Hotez PJ, Bottazzi ME, Craig SL, Jones KM. Reproductive Outcomes in Rhesus Macaques ( Macaca mulatta) with Naturally-acquired Trypanosoma cruzi Infection. Comp Med 2020; 70:152-159. [PMID: 32183928 DOI: 10.30802/aalas-cm-19-000077] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Chagas disease is a zoonotic vector-borne disease caused by infection with the protozoan parasite Trypanosoma cruzi. T. cruzi is found in Latin America and the Southern United States, where it infects many species, including humans and nonhuman primates (NHPs). NHPs are susceptible to natural infection and can develop clinical symptoms consistent with human disease, including Chagasic cardiomyopathy, gastrointestinal disease and transplacental transmission, leading to congenital infection. Due to evidence of Chagas transmission in Texas, this study hypothesized T. cruzi infection was present in a closed, outdoor-housed breeding colony of rhesus macaques (Macaca mulatta) located at a biomedical research facility in Central Texas. In addition, we questioned whether seropositive female rhesus macaques might experience reproductive complications consistent with maternal-fetal Chagas disease. The seroprevalence of T. cruzi infection in the colony was assessed using an Enzyme Linked Immunosorbant Assay (ELISA) to detect antibodies against Tc24 antigen as a screening assay, and a commercially available immunochromatographic test (Chagas Stat Pak) as a confirmatory assay. Retrospective serologic analysis was performed to confirm the status of all T. cruzi-infected animals between the years 2012 to 2016. The medical history of all seropositive and seronegative breeding females within the colony from 2012 to 2016 was reviewed to determine each animals' level of reproductive fitness. The percentage of T. cruzi-seropositive animals ranged from 6.7% to 9.7% in adult animals and 0% to 0.44% in juveniles or weanling animals, depending on the year. An overall 3.9% seroprevalence of T. cruzi infection was found in the total population. No significant differences in any measure of reproductive outcomes were identified between seropositive and seronegative females from 2012 to 2016. The lack of significant adverse reproductive outcomes reported here may help inform future management decisions regarding seropositive female rhesus macaques within breeding colonies.
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Affiliation(s)
- April L Kendricks
- Southwest Electronic Energy Medical Research Institute, Houston, Texas; Baylor College of Medicine, Houston, Texas;,
| | - Stanton B Gray
- The University of Texas MD Anderson Cancer Center, Michale E. Keeling Center for Comparative Medicine, Bastrop, Texas
| | - Gregory K Wilkerson
- The University of Texas MD Anderson Cancer Center, Michale E. Keeling Center for Comparative Medicine, Bastrop, Texas
| | | | - Christian R Abee
- The University of Texas MD Anderson Cancer Center, Michale E. Keeling Center for Comparative Medicine, Bastrop, Texas
| | | | - Peter J Hotez
- Baylor College of Medicine, Houston, Texas; National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas; Texas Children's Hospital Center for Vaccine Development, Houston, Texas; Department of Biology, Baylor University, Waco, Texas
| | - Maria Elena Bottazzi
- Baylor College of Medicine, Houston, Texas; National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas; Texas Children's Hospital Center for Vaccine Development, Houston, Texas; Department of Biology, Baylor University, Waco, Texas
| | - Suzanne L Craig
- Medical University of South Carolina, Charleston, South Carolina
| | - Kathryn M Jones
- Baylor College of Medicine, Houston, Texas; National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas
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27
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Abstract
American trypanosomiasis is caused by a parasite endemic of the Americas. Current migration has globalized Chagas disease. Acute infection usually resolves spontaneously. Nonetheless, 20% to 40% develop cardiomyopathy 20 to 30 years later. Progression to cardiomyopathy is devastatingly rapid, manifesting with heart failure and sudden death. Etiologic treatment is highly effective and recommended in those with acute infections, congenital infections, and parasite reactivation, and women of childbearing age, but in asymptomatic Trypanosoma cruzi carriers and patients with early cardiomyopathy remains controversial and under investigation. Progression of heart failure is rapid and accounts for most of the morbidity and related mortality.
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Affiliation(s)
- Luis E Echeverria
- Grupo de Estudios Epidemiológicos y Salud Pública, Heart Failure and Heart Transplant Clinic, Fundacion Cardiovascular de Colombia, Calle 155 A No. 23-58, Urbanizacion El Bosque, Floridablanca, Santander, Colombia
| | - Carlos A Morillo
- Division of Cardiology, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Foothills Medical Centre, Room C823, 1403 29th Street Northwest, Calgary, Alberta T2N 2T9, Canada.
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28
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Norman FF, López-Vélez R. Chagas disease: comments on the 2018 PAHO Guidelines for diagnosis and management. J Travel Med 2019; 26:5549353. [PMID: 31407784 DOI: 10.1093/jtm/taz060] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 07/24/2019] [Accepted: 08/01/2019] [Indexed: 01/12/2023]
Abstract
BACKGROUND Chagas disease, or American trypanosomiasis, is a protozoan infectious disease endemic throughout most of the Americas, caused by the trypanosome, Trypanosoma cruzi, and mainly transmitted to humans by reduviid or kissing bugs. Some progress has been achieved in control of the disease mainly in endemic areas, but migration flows have acted as drivers for the emergence of the disease mainly in non-endemic areas of Europe and North America. Most imported cases of Chagas disease in Europe are reported in migrants from highly endemic areas of countries such as Bolivia and Paraguay, and reports of Chagas disease in travellers are extremely rare. METHODS Pan American Health Organization (PAHO) recently updated their guidelines on the diagnosis and management of Chagas. These guidelines and their applicability to migrants and travellers are reviewed. RESULTS PAHO recommends the use of two serological tests for diagnosis of chronic infection (allowing for the use of a single sensitive test followed by confirmation in special settings such as the screening of potential blood donors). The indication for specific trypanocidal treatment of acute infections, children and women of child-bearing age remains as before, with either benznidazole or nifurtimox being the treatment of choice. For chronic infection with/without organ damage, treatment recommendations are less well defined. Although treatment is generally not recommended in patients with visceral involvement, decisions regarding treatment need to be tailored to the individual. Either benznidazole or nifurtimox may be used for initial treatment. CONCLUSIONS The recent PAHO Guidelines provide a framework to aid the diagnosis and management of this infection, but several aspects such as the underdiagnosis of infections, the multidisciplinary approach to patient management, the investigation of novel biomarkers of disease progression/response to treatment and the development of new treatment strategies are areas which should be further strengthened.
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Affiliation(s)
- Francesca F Norman
- National Referral Unit for Tropical Diseases, Infectious Diseases Department, Ramón y Cajal University Hospital, IRYCIS, Ctra Colmenar, Km 9,100, 28034, Madrid, Spain
| | - Rogelio López-Vélez
- National Referral Unit for Tropical Diseases, Infectious Diseases Department, Ramón y Cajal University Hospital, IRYCIS, Ctra Colmenar, Km 9,100, 28034, Madrid, Spain
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Lidani KCF, Andrade FA, Bavia L, Damasceno FS, Beltrame MH, Messias-Reason IJ, Sandri TL. Chagas Disease: From Discovery to a Worldwide Health Problem. Front Public Health 2019; 7:166. [PMID: 31312626 PMCID: PMC6614205 DOI: 10.3389/fpubh.2019.00166] [Citation(s) in RCA: 326] [Impact Index Per Article: 54.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 06/05/2019] [Indexed: 12/23/2022] Open
Abstract
Carlos Chagas discovered American trypanosomiasis, also named Chagas disease (CD) in his honor, just over a century ago. He described the clinical aspects of the disease, characterized by its etiological agent (Trypanosoma cruzi) and identified its insect vector. Initially, CD occurred only in Latin America and was considered a silent and poorly visible disease. More recently, CD became a neglected worldwide disease with a high morbimortality rate and substantial social impact, emerging as a significant public health threat. In this context, it is crucial to better understand better the epidemiological scenarios of CD and its transmission dynamics, involving people infected and at risk of infection, diversity of the parasite, vector species, and T. cruzi reservoirs. Although efforts have been made by endemic and non-endemic countries to control, treat, and interrupt disease transmission, the cure or complete eradication of CD are still topics of great concern and require global attention. Considering the current scenario of CD, also affecting non-endemic places such as Canada, USA, Europe, Australia, and Japan, in this review we aim to describe the spread of CD cases worldwide since its discovery until it has become a global public health concern.
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Affiliation(s)
| | - Fabiana Antunes Andrade
- Laboratory of Molecular Immunopathology, Clinical Hospital, Federal University of Paraná, Curitiba, Brazil
| | - Lorena Bavia
- Laboratory of Molecular Immunopathology, Clinical Hospital, Federal University of Paraná, Curitiba, Brazil
| | - Flávia Silva Damasceno
- Laboratory of Biochemistry of Tryps-LaBTryps, Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Marcia Holsbach Beltrame
- Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná, Curitiba, Brazil
| | - Iara J. Messias-Reason
- Laboratory of Molecular Immunopathology, Clinical Hospital, Federal University of Paraná, Curitiba, Brazil
| | - Thaisa Lucas Sandri
- Laboratory of Molecular Immunopathology, Clinical Hospital, Federal University of Paraná, Curitiba, Brazil
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
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Angheben A, Buonfrate D, Cruciani M, Jackson Y, Alonso-Padilla J, Gascon J, Gobbi F, Giorli G, Anselmi M, Bisoffi Z. Rapid immunochromatographic tests for the diagnosis of chronic Chagas disease in at-risk populations: A systematic review and meta-analysis. PLoS Negl Trop Dis 2019; 13:e0007271. [PMID: 31150377 PMCID: PMC6561601 DOI: 10.1371/journal.pntd.0007271] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 06/12/2019] [Accepted: 02/28/2019] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Despite of a high disease burden, mainly in Latin America, Chagas disease (CD) is underdiagnosed and undertreated. Rapid diagnostic tests (RDTs) might improve the access to diagnosis. The aim of this study is to review the accuracy of commercially available RDTs used in field conditions for the diagnosis of chronic CD in populations at risk, in endemic and non-endemic countries. METHODS/PRINCIPAL FINDINGS We undertook a comprehensive search of the following databases: PubMed, SCOPUS, LILACS (last up-date on the 01st July, 2017), without language or date limits. Non-electronic sources have been also searched. This review included clinical studies with cohort recruitment of individuals at risk of T. cruzi exposure, without age limits; adequate reference standards for the diagnosis of CD. We excluded case-control studies and those testing RDTs during acute CD. Data on test accuracies were pooled through a bivariate random-effects model. Only one index test was evaluated separately. Geographical area, commercial brand, disease prevalence, study size, and risk of bias were explored as possible source of heterogeneity. Values of sensitivity and specificity were computed to obtain summary positive/negative likelihood ratios, and summary diagnostic odds ratio. Ten studies were included on six different immunochromatographic RDTs. The pooled sensitivity and specificity of the RDTs resulted 96.6% (95% CI 91.3-98.7%) and 99.3% (95% CI 98.4-99.7%), respectively. Test accuracy was particularly good in endemic areas (98.07%/99.03% of sensitivity/specificity, respectively). One test (Stat-Pak) showed an overall sensitivity of 97% (95% CI 87.6-99.3) and specificity of 99.4% (95% CI 98.6-99.8). CONCLUSIONS/SIGNIFICANCE RDTs demonstrated to be sufficiently accurate to recommend their use for screening in endemic areas, even as stand-alone tests. This approach might increase the accessibility to the diagnosis. However, an additional confirmatory test in case of positive result remains a prudent approach.
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Affiliation(s)
- Andrea Angheben
- Department of Infectious – Tropical Diseases and Microbiology, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar, Verona, Italy
| | - Dora Buonfrate
- Department of Infectious – Tropical Diseases and Microbiology, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar, Verona, Italy
| | - Mario Cruciani
- Infectious Diseases Unit, Azienda ULSS 9 Scaligera, Verona, Italy
| | - Yves Jackson
- Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland
- Institute of Global Health, Geneva University, Geneva, Switzerland
| | | | - Joaquim Gascon
- ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
| | - Federico Gobbi
- Department of Infectious – Tropical Diseases and Microbiology, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar, Verona, Italy
| | - Giovanni Giorli
- Department of Infectious – Tropical Diseases and Microbiology, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar, Verona, Italy
| | - Mariella Anselmi
- Centro de Epidemiologia Comunitaria y Medicina Tropical (CECOMET), Esmeraldas, Ecuador
| | - Zeno Bisoffi
- Department of Infectious – Tropical Diseases and Microbiology, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar, Verona, Italy
- Diagnostic and Public Health Department, University of Verona, Verona, Italy
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Pacheco AL, Vicentini G, Matteucci KC, Ribeiro RR, Weinlich R, Bortoluci KR. The impairment in the NLRP3-induced NO secretion renders astrocytes highly permissive to T. cruzi replication. J Leukoc Biol 2019; 106:201-207. [PMID: 30997938 DOI: 10.1002/jlb.4ab1118-416rr] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 03/27/2019] [Accepted: 03/28/2019] [Indexed: 12/18/2022] Open
Abstract
Trypanossoma cruzi (T. cruzi), the causative protozoan of Chagas disease (CD) invades many cell types, including central nervous system (CNS) cells triggering local lesions and neurological impact. Previous work from our group described NLRP3 inflammasomes as central effectors for the parasite control by macrophages. Recent evidences demonstrate that NLRP3 can be activated in CNS cells with controversial consequences to the control of infections and inflammatory pathologies. However, the relative contribution of NLRP3 in different cell types remains to be elucidated. In this article, we described an effector response mediated by NLRP3 that works on microglia but not on astrocytes to control T. cruzi infection. Despite T. cruzi ability to invade astrocytes and microglia, astrocytes were clearly more permissive to parasite replication. Moreover, the absence of NLRP3 renders microglia but not astrocytes more permissive to T. cruzi replication. In fact, microglia but not astrocytes were able to secrete NLRP3-dependent IL-1β and NO in response to T. cruzi. Importantly, the pharmacological inhibition of iNOS with aminoguanidine resulted in a significant increase in the numbers of amastigotes found in microglia from wild-type but not from NLRP3-/- mice, indicating the importance of NLRP3-mediated NO secretion to the infection control by these cells. Taken together, our findings revealed that T. cruzi differentially activates NLRP3 inflammasomes in astrocytes and microglia and established a role for these platforms in the control of a protozoan infection by glial cells from CNS.
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Affiliation(s)
- Aline L Pacheco
- Departamento de Ciências Biológicas e Centro de Terapia Celular e Molecular (CTC-Mol), UNIFESP, São Paulo, Brazil
| | - Gabriella Vicentini
- Departamento de Ciências Biológicas e Centro de Terapia Celular e Molecular (CTC-Mol), UNIFESP, São Paulo, Brazil
| | - Kely C Matteucci
- Departamento de Ciências Biológicas e Centro de Terapia Celular e Molecular (CTC-Mol), UNIFESP, São Paulo, Brazil
| | - Rafaela Rosa Ribeiro
- Instituto de Ensino e Pesquisa, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Ricardo Weinlich
- Instituto de Ensino e Pesquisa, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Karina R Bortoluci
- Departamento de Ciências Biológicas e Centro de Terapia Celular e Molecular (CTC-Mol), UNIFESP, São Paulo, Brazil
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Pereiro AC. Guidelines for the diagnosis and treatment of Chagas disease. Lancet 2019; 393:1486-1487. [PMID: 30983574 DOI: 10.1016/s0140-6736(19)30288-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 01/28/2019] [Indexed: 10/27/2022]
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Arnal A, Waleckx E, Rico-Chávez O, Herrera C, Dumonteil E. Estimating the current burden of Chagas disease in Mexico: A systematic review and meta-analysis of epidemiological surveys from 2006 to 2017. PLoS Negl Trop Dis 2019; 13:e0006859. [PMID: 30964871 PMCID: PMC6474657 DOI: 10.1371/journal.pntd.0006859] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 04/19/2019] [Accepted: 03/15/2019] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND In Mexico, estimates of Chagas disease prevalence and burden vary widely. Updating surveillance data is therefore an important priority to ensure that Chagas disease does not remain a barrier to the development of Mexico's most vulnerable populations. METHODOLOGY/PRINCIPAL FINDINGS The aim of this systematic review and meta-analysis was to analyze the literature on epidemiological surveys to estimate Chagas disease prevalence and burden in Mexico, during the period 2006 to 2017. A total of 2,764 articles were screened and 36 were retained for the final analysis. Epidemiological surveys have been performed in most of Mexico, but with variable study scale and geographic coverage. Based on studies reporting confirmed cases (i.e. using at least 2 serological tests), and taking into account the differences in sample sizes, the national estimated seroprevalence of Trypanosoma cruzi infection was 3.38% [95%CI 2.59-4.16], suggesting that there are 4.06 million cases in Mexico. Studies focused on pregnant women, which may transmit the parasite to their newborn during pregnancy, reported an estimated seroprevalence of 2.21% [95%CI 1.46-2.96], suggesting that there are 50,675 births from T. cruzi infected pregnant women per year, and 3,193 cases of congenitally infected newborns per year. Children under 18 years had an estimated seropositivity rate of 1.51% [95%CI 0.77-2.25], which indicate ongoing transmission. Cases of T. cruzi infection in blood donors have also been reported in most states, with a national estimated seroprevalence of 0.55% [95%CI 0.43-0.66]. CONCLUSIONS/SIGNIFICANCE Our analysis suggests a disease burden for T. cruzi infection higher than previously recognized, highlighting the urgency of establishing Chagas disease surveillance and control as a key national public health priority in Mexico, to ensure that it does not remain a major barrier to the economic and social development of the country's most vulnerable populations.
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Affiliation(s)
- Audrey Arnal
- Departamento de Ecología de la Biodiversidad, Instituto de Ecología, Universidad Nacional Autónoma de México, Ciudad de México, México
- Centro de Investigaciones Regionales Dr Hideyo Noguchi, Universidad Autónoma de Yucatán, calle 96 s/n x av. Jacinto Canek y calle 47, Col. Paseo de las Fuentes, CP 97225, Mérida, Yucatán, México
| | - Etienne Waleckx
- Centro de Investigaciones Regionales Dr Hideyo Noguchi, Universidad Autónoma de Yucatán, calle 96 s/n x av. Jacinto Canek y calle 47, Col. Paseo de las Fuentes, CP 97225, Mérida, Yucatán, México
- Institut de Recherche pour le Développement, UMR INTERTRYP IRD, CIRAD, Université de Montpellier, Montpellier, France
| | - Oscar Rico-Chávez
- Departamento de Etología, Fauna Silvestre y Animales de Laboratorio, Facultad de Medicina Veterinaria Zootecnia, Universidad Nacional Autónoma de México, 04510 Ciudad de México, México
| | - Claudia Herrera
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, 1440 Canal St., New Orleans, LA 70112, United States of America
| | - Eric Dumonteil
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, 1440 Canal St., New Orleans, LA 70112, United States of America
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Egui A, Lasso P, Pérez-Antón E, Thomas MC, López MC. Dynamics of T Cells Repertoire During Trypanosoma cruzi Infection and its Post-Treatment Modulation. Curr Med Chem 2018; 26:6519-6543. [PMID: 30381063 DOI: 10.2174/0929867325666181101111819] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 09/11/2018] [Accepted: 09/25/2018] [Indexed: 01/16/2023]
Abstract
Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host's immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.
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Affiliation(s)
- Adriana Egui
- Instituto de Parasitologia y Biomedicina Lopez-Neyra, Consejo Superior de Investigaciones Científicas; Granada, Spain
| | - Paola Lasso
- Grupo de Inmunobiologia y Biologia Celular, Pontificia Universidad Javeriana; Bogota, Colombia
| | - Elena Pérez-Antón
- Instituto de Parasitologia y Biomedicina Lopez-Neyra, Consejo Superior de Investigaciones Científicas; Granada, Spain
| | - M Carmen Thomas
- Instituto de Parasitologia y Biomedicina Lopez-Neyra, Consejo Superior de Investigaciones Científicas; Granada, Spain
| | - Manuel Carlos López
- Instituto de Parasitologia y Biomedicina Lopez-Neyra, Consejo Superior de Investigaciones Científicas; Granada, Spain
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Cockram PE, Smith TK. Active Natural Product Scaffolds against Trypanosomatid Parasites: A Review. JOURNAL OF NATURAL PRODUCTS 2018; 81:2138-2154. [PMID: 30234295 DOI: 10.1021/acs.jnatprod.8b00159] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Neglected tropical diseases caused by trypanosomatid parasites are a continuing and escalating problem, which devastate the less economically developed cultures in countries in which they are endemic by impairing both human and animal health. Current drugs for these diseases are regarded as out-of-date and expensive, with unacceptable side-effects and mounting parasite resistance, meaning there is an urgent need for new therapeutics. Natural products have long been a source of potent, structurally diverse bioactive molecules. Herein are reviewed natural products with reported trypanocidal activity, which have been clustered based on core structural similarities, to aid the future discovery of new trypanocidal core motifs with potential routes to synthetically accessible natural product cores suggested.
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Affiliation(s)
- Peter E Cockram
- Biomedical Sciences Research Complex , University of St Andrews , North Haugh , St Andrews , Scotland , KY16 9ST
| | - Terry K Smith
- Biomedical Sciences Research Complex , University of St Andrews , North Haugh , St Andrews , Scotland , KY16 9ST
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Gunter SM, Versteeg L, Jones KM, Keegan BP, Strych U, Bottazzi ME, Hotez PJ, Brown EL. Covalent vaccination with Trypanosoma cruzi Tc24 induces catalytic antibody production. Parasite Immunol 2018; 40:e12585. [PMID: 30132929 DOI: 10.1111/pim.12585] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 08/13/2018] [Accepted: 08/16/2018] [Indexed: 11/28/2022]
Abstract
Trypanosoma cruzi 24 (Tc24) is a recently described B-cell superantigen (BC-SAg) expressed by all developmental stages of T. cruzi, the causative agent of Chagas disease. BC-SAgs are immunoevasins that interfere with the catalytic response available to a subset of natural antibodies comprising the preimmune (innate) repertoire. Electrophilic modifications of BC-SAgs facilitate the formation of highly energetic covalent reactions favouring B-cell differentiation instead of B-cell downregulation. Therefore, the aim of this study was to convert the inhibitory signals delivered to B-cells with specificity for Tc24 into activating signals after conjugating electrophilic phosphonate groups to recombinant Tc24 (eTc24). Covalent immunization with eTc24 increased the binding affinity between eTc24 and naturally nucleophilic immunoglobulins with specificity for this BC-SAg. Flow cytometric analyses demonstrated that eTc24 but not Tc24 or other electrophilically modified control proteins bound Tc24-specific IgM+ B-cells covalently. In addition, immunization of mice with eTc24 adjuvanted with ISA720 induced the production of catalytic responses specific for Tc24 compared to the abrogation of this response in mice immunized with Tc24/ISA720. eTc24-immunized mice also produced IgMs that bound recombinant Tc24 compared to the binding observed for IgMs purified from non eTc24-immunized controls. These data suggest that eTc24 immunization overrides the immunosuppressive properties of this BC-SAg.
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Affiliation(s)
- Sarah M Gunter
- Texas Children's Hospital Center for Vaccine Development, Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas
| | - Leroy Versteeg
- Texas Children's Hospital Center for Vaccine Development, Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas
| | - Kathryn M Jones
- Texas Children's Hospital Center for Vaccine Development, Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas
| | - Brian P Keegan
- Texas Children's Hospital Center for Vaccine Development, Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas
| | - Ulrich Strych
- Texas Children's Hospital Center for Vaccine Development, Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas
| | - Maria Elena Bottazzi
- Texas Children's Hospital Center for Vaccine Development, Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas.,Department of Biology, Baylor University, Waco, Texas
| | - Peter J Hotez
- Texas Children's Hospital Center for Vaccine Development, Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas
| | - Eric L Brown
- Center for Infectious Disease, The University of Texas School of Public Health, Houston, Texas
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Costa HS, Lima MMO, Figueiredo PHS, Chaves AT, Nunes MCP, da Costa Rocha MO. The prognostic value of health-related quality of life in patients with Chagas heart disease. Qual Life Res 2018; 28:67-72. [PMID: 30167935 DOI: 10.1007/s11136-018-1980-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2018] [Indexed: 01/04/2023]
Abstract
PURPOSE To verify the prognostic value of health-related quality of life (HRQoL) and the differences in HRQoL and clinical variables between groups of Chagas heart disease (CHD) patients with and without cardiovascular adverse events. METHODS Seventy-five CHD patients were evaluated by echocardiography, maximal exercise testing, and Short-form of Health Survey (SF-36) Questionnaire. Patients were followed during 6 years. In the statistical analysis, uni- and multivariate Cox regression were performed to verify the accuracy of the HRQoL in predicting cardiovascular events. RESULTS After the follow-up period (41 ± 12 months), 20 patients (27%) had adverse events. Those with poor outcome had lower left ventricular ejection fraction (LVEF) (p = 0.002), higher left ventricular end-diastolic diameter (LVDd) (p = 0.019), and worse scores in general health perceptions (p = 0.047), social role functioning (p = 0.026), and mental component summary (p = 0.043) of SF-36. Patients with lower LVEF (p = 0.003), higher LVDd (p = 0.022), worse HRQoL in the general heath perceptions domain (p = 0.022), and mental component summary (p = 0.031) were associated with worse prognosis. In the multivariate Cox regression, LVEF (HR 0.94, 95% CI from 0.90 to 0.98, p = 0.007) and mental component summary (HR 0.98, 95% CI from 0.94 to 1.00, p = 0.047) remained as independent predictors of adverse events in CHD patients. CONCLUSION The assessment of HRQoL, especially the mental component, should be taken into account to provide an accurate prognosis in addition to other well-established predictors of poor outcomes in CHD patients.
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Affiliation(s)
- Henrique Silveira Costa
- Postgraduate Course of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical School and Hospital das Clinicas of the Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30.130-100, Brazil.
| | - Márcia Maria Oliveira Lima
- Healthy and Biological Sciences Faculty, Physical Therapy School, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Pedro Henrique Scheidt Figueiredo
- Healthy and Biological Sciences Faculty, Physical Therapy School, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
| | - Ana Thereza Chaves
- Postgraduate Course of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical School and Hospital das Clinicas of the Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30.130-100, Brazil
| | - Maria Carmo Pereira Nunes
- Postgraduate Course of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical School and Hospital das Clinicas of the Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30.130-100, Brazil
| | - Manoel Otávio da Costa Rocha
- Postgraduate Course of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical School and Hospital das Clinicas of the Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30.130-100, Brazil
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Waleckx E, Pérez-Carrillo S, Chávez-Lazo S, Pasos-Alquicira R, Cámara-Heredia M, Acuña-Lizama J, Collí-Balám F, Cámara-Mejía J, Ramírez-Sierra MJ, Cruz-Chan V, Rosado-Vallado M, Vázquez-Narvaez S, Najera-Vázquez R, Gourbière S, Dumonteil E. Non-randomized controlled trial of the long-term efficacy of an Ecohealth intervention against Chagas disease in Yucatan, Mexico. PLoS Negl Trop Dis 2018; 12:e0006605. [PMID: 29965992 PMCID: PMC6044551 DOI: 10.1371/journal.pntd.0006605] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 07/13/2018] [Accepted: 06/12/2018] [Indexed: 11/18/2022] Open
Abstract
Non-domiciliated intrusive triatomine vectors are responsible for a low but significant transmission of Trypanosoma cruzi to humans. Their control is a challenge as insecticide spraying is of limited usefulness, and alternative strategies need to be developed for a sustainable control. We performed a non-randomized controlled trial of an Ecohealth intervention based on window insect screens and community participation to reduce house infestation by Triatoma dimidiata in two rural villages in Yucatan, Mexico. Efficacy of the intervention was measured over a three years follow-up period and entomological indicators showed that the proportion of triatomines found inside houses was significantly reduced in houses with insect screens, which effectively kept more bugs on the outside of houses. Using a previously developed model linking entomological data to the prevalence of infection in human, we predicted that the intervention would lead to a 32% reduction in yearly incidence and in the prevalence of T. cruzi infection. The cost for the coverage of all the windows of a house was of comparable magnitude to what families currently spend on various domestic insecticide, and most screens were still in good conditions after three years. In conclusion, the Ecohealth approach proposed here is effective for the long-term and sustainable control of intrusive T. dimidiata vectors in the Yucatan peninsula, Mexico. This strategy may also be easily adapted to other intrusive triatomine species as well as other regions/countries with comparable eco-epidemiological settings, and would be an excellent component of a larger integrated program for the control of a variety of other vector-borne diseases, bringing additional benefits to the communities. Our results should encourage a further scaling-up of our implementation strategy in additional villages in the region.
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Affiliation(s)
- Etienne Waleckx
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Silvia Pérez-Carrillo
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Samuel Chávez-Lazo
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Rafael Pasos-Alquicira
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - María Cámara-Heredia
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Jesús Acuña-Lizama
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Fernando Collí-Balám
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Javier Cámara-Mejía
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Maria Jesús Ramírez-Sierra
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Vladimir Cruz-Chan
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Miguel Rosado-Vallado
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | - Santos Vázquez-Narvaez
- Departamento de Control de Vectores, Servicios de Salud de Yucatán, Mérida, Yucatán, Mexico
| | - Rosario Najera-Vázquez
- Departamento de Control de Vectores, Servicios de Salud de Yucatán, Mérida, Yucatán, Mexico
| | - Sébastien Gourbière
- UMR 5096 ‘Laboratoire Génome et Développement des Plantes’, Université de Perpignan Via Domitia, Perpignan, France
| | - Eric Dumonteil
- Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
- Department of Tropical Medicine, Vector-Borne and Infectious Disease Research Center, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States of America
- * E-mail:
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Stillwaggon E, Perez-Zetune V, Bialek SR, Montgomery SP. Congenital Chagas Disease in the United States: Cost Savings through Maternal Screening. Am J Trop Med Hyg 2018; 98:1733-1742. [PMID: 29714163 PMCID: PMC6086189 DOI: 10.4269/ajtmh.17-0818] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors through transfusions, transplants, insect feces in food, and from mother to child during gestation. Congenital infection could perpetuate Chagas disease indefinitely, even in countries without vector transmission. An estimated 30% of infected persons will develop lifelong, potentially fatal, cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment of Chagas disease in the United States. We constructed a decision-analytic model to find the lower cost option, comparing costs of testing and treatment, as needed, for mothers and infants with the lifetime societal costs without testing and the consequent morbidity and mortality due to lack of treatment or late treatment. We found that maternal screening, infant testing, and treatment of Chagas disease in the United States are cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence above 0.06% compared with no screening program. Newly approved diagnostics make universal screening cost saving with maternal prevalence as low as 0.008%. The present value of lifetime societal savings due to screening and treatment is about $634 million saved for every birth year cohort. The benefits of universal screening for T. cruzi as part of routine prenatal testing far outweigh the program costs for all U.S. births.
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Affiliation(s)
| | - Victoria Perez-Zetune
- International Finance Division, Board of Governors of the Federal Reserve System, Washington, District of Columbia
| | - Stephanie R Bialek
- Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Susan P Montgomery
- Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
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Mast cell-nerve interaction in the colon of Trypanosoma cruzi-infected individuals with chagasic megacolon. Parasitol Res 2018; 117:1147-1158. [PMID: 29470711 DOI: 10.1007/s00436-018-5792-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 01/29/2018] [Indexed: 12/16/2022]
Abstract
Chagas disease is an infection caused by the parasite Trypanosoma cruzi that affects millions of people worldwide and is endemic in Latin America. Megacolon is the most frequent complication of the digestive chronic form and happens due to lesions of the enteric nervous system. The neuronal lesions seem to initiate in the acute phase and persist during the chronic phase, albeit the mechanisms involved in this process are still debated. Among the cells of the immune system possibly involved in this pathological process is the mast cell (MC) due to its well-known role in the bi-directional communication between the immune and nervous systems. Using ultrastructural analysis, we found an increased number of degranulated MCs in close proximity to nerve fibers in infected patients when compared with uninfected controls. We also immunostained MCs for the two pro-inflammatory molecules tryptase and chymase, the first being also important in neuronal death. The number of MCs immunostained for tryptase or chymase was increased in patients with megacolon, whereas increased tryptase staining was additionally observed in patients without megacolon. Moreover, we detected the expression of the tryptase receptor PAR2 in neurons of the enteric nervous system, which correlated to the tryptase staining results. Altogether, the data presented herein point to the participation of MCs on the denervation process that occurs in the development of T. cruzi-induced megacolon.
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Keller JI, Ballif BA, St. Clair RM, Vincent JJ, Monroy MC, Stevens L. Chagas disease vector blood meal sources identified by protein mass spectrometry. PLoS One 2017; 12:e0189647. [PMID: 29232402 PMCID: PMC5726658 DOI: 10.1371/journal.pone.0189647] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 11/29/2017] [Indexed: 02/08/2023] Open
Abstract
Chagas disease is a complex vector borne parasitic disease involving blood feeding Triatominae (Hemiptera: Reduviidae) insects, also known as kissing bugs, and the vertebrates they feed on. This disease has tremendous impacts on millions of people and is a global health problem. The etiological agent of Chagas disease, Trypanosoma cruzi (Kinetoplastea: Trypanosomatida: Trypanosomatidae), is deposited on the mammalian host in the insect’s feces during a blood meal, and enters the host’s blood stream through mucous membranes or a break in the skin. Identifying the blood meal sources of triatomine vectors is critical in understanding Chagas disease transmission dynamics, can lead to identification of other vertebrates important in the transmission cycle, and aids management decisions. The latter is particularly important as there is little in the way of effective therapeutics for Chagas disease. Several techniques, mostly DNA-based, are available for blood meal identification. However, further methods are needed, particularly when sample conditions lead to low-quality DNA or to assess the risk of human cross-contamination. We demonstrate a proteomics-based approach, using liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify host-specific hemoglobin peptides for blood meal identification in mouse blood control samples and apply LC-MS/MS for the first time to Triatoma dimidiata insect vectors, tracing blood sources to species. In contrast to most proteins, hemoglobin, stabilized by iron, is incredibly stable even being preserved through geologic time. We compared blood stored with and without an anticoagulant and examined field-collected insect specimens stored in suboptimal conditions such as at room temperature for long periods of time. To our knowledge, this is the first study using LC-MS/MS on field-collected arthropod disease vectors to identify blood meal composition, and where blood meal identification was confirmed with more traditional DNA-based methods. We also demonstrate the potential of synthetic peptide standards to estimate relative amounts of hemoglobin acquired when insects feed on multiple blood sources. These LC-MS/MS methods can contribute to developing Ecohealth control strategies for Chagas disease transmission and can be applied to other arthropod disease vectors.
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Affiliation(s)
- Judith I. Keller
- Department of Biology, University of Vermont, Burlington, Vermont, United States of America
| | - Bryan A. Ballif
- Department of Biology, University of Vermont, Burlington, Vermont, United States of America
- * E-mail: (LS); (BAB)
| | - Riley M. St. Clair
- Department of Biology, University of Vermont, Burlington, Vermont, United States of America
| | - James J. Vincent
- Department of Biology, University of Vermont, Burlington, Vermont, United States of America
| | - M. Carlota Monroy
- Department of Biology, University of Vermont, Burlington, Vermont, United States of America
- Laboratorio de Entomología Aplicada y Parasitología, Escuela de Biología, Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Ciudad de Guatemala, Guatemala
| | - Lori Stevens
- Department of Biology, University of Vermont, Burlington, Vermont, United States of America
- * E-mail: (LS); (BAB)
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Dawidowski M, Emmanouilidis L, Kalel VC, Tripsianes K, Schorpp K, Hadian K, Kaiser M, Mäser P, Kolonko M, Tanghe S, Rodriguez A, Schliebs W, Erdmann R, Sattler M, Popowicz GM. Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites. Science 2017; 355:1416-1420. [PMID: 28360328 DOI: 10.1126/science.aal1807] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 03/09/2017] [Indexed: 12/14/2022]
Abstract
The parasitic protists of the Trypanosoma genus infect humans and domestic mammals, causing severe mortality and huge economic losses. The most threatening trypanosomiasis is Chagas disease, affecting up to 12 million people in the Americas. We report a way to selectively kill Trypanosoma by blocking glycosomal/peroxisomal import that depends on the PEX14-PEX5 protein-protein interaction. We developed small molecules that efficiently disrupt the PEX14-PEX5 interaction. This results in mislocalization of glycosomal enzymes, causing metabolic catastrophe, and it kills the parasite. High-resolution x-ray structures and nuclear magnetic resonance data enabled the efficient design of inhibitors with trypanocidal activities comparable to approved medications. These results identify PEX14 as an "Achilles' heel" of the Trypanosoma suitable for the development of new therapies against trypanosomiases and provide the structural basis for their development.
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Affiliation(s)
- M Dawidowski
- Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.,Center for Integrated Protein Science Munich at Chair of Biomolecular NMR, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany
| | - L Emmanouilidis
- Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.,Center for Integrated Protein Science Munich at Chair of Biomolecular NMR, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany
| | - V C Kalel
- Institute of Biochemistry and Pathobiochemistry, Department of Systems Biochemistry, Faculty of Medicine, Ruhr University Bochum, 44780 Bochum, Germany
| | - K Tripsianes
- CEITEC, Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
| | - K Schorpp
- Assay Development and Screening Platform, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
| | - K Hadian
- Assay Development and Screening Platform, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
| | - M Kaiser
- Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland.,University of Basel, 4001 Basel, Switzerland
| | - P Mäser
- Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland.,University of Basel, 4001 Basel, Switzerland
| | - M Kolonko
- Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
| | - S Tanghe
- New York University School of Medicine, Department of Microbiology, 341 East 25th Street, Room 513, New York, NY 10010, USA
| | - A Rodriguez
- New York University School of Medicine, Department of Microbiology, 341 East 25th Street, Room 513, New York, NY 10010, USA
| | - W Schliebs
- Institute of Biochemistry and Pathobiochemistry, Department of Systems Biochemistry, Faculty of Medicine, Ruhr University Bochum, 44780 Bochum, Germany
| | - R Erdmann
- Institute of Biochemistry and Pathobiochemistry, Department of Systems Biochemistry, Faculty of Medicine, Ruhr University Bochum, 44780 Bochum, Germany.
| | - M Sattler
- Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. .,Center for Integrated Protein Science Munich at Chair of Biomolecular NMR, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany
| | - G M Popowicz
- Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. .,Center for Integrated Protein Science Munich at Chair of Biomolecular NMR, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany
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Soto-Becerra R, Bazan V, Bautista W, Malavassi F, Altamar J, Ramirez JD, Everth A, Callans DJ, Marchlinski FE, Rodríguez D, García FC, Sáenz LC. Ventricular Tachycardia in the Setting of Chagasic Cardiomyopathy. Circ Arrhythm Electrophysiol 2017; 10:CIRCEP.116.004950. [DOI: 10.1161/circep.116.004950] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 09/18/2017] [Indexed: 11/16/2022]
Affiliation(s)
- Richard Soto-Becerra
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - Victor Bazan
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - William Bautista
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - Federico Malavassi
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - Jhancarlo Altamar
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - Juan David Ramirez
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - Arlen Everth
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - David J. Callans
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - Francis E. Marchlinski
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - Diego Rodríguez
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - Fermin C. García
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
| | - Luis C. Sáenz
- From the International Arrhythmia Center at CardioInfantil Foundation-Cardiac Institute, Bogotá, Colombia (R.S.-B., W.B., F.M., J.A., J.D.R., A.E., D.R., L.C.S.); Electrophysiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (V.B.); and Division of Cardiology, Electrophysiology Program, Hospital of the University of Pennsylvania, Philadelphia (D.J.C., F.E.M., F.C.G.)
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Chambela MC, Mediano MFF, Ferreira RR, Japiassú AM, Waghabi MC, da Silva GMS, Saraiva RM. Correlation of 6-min walk test with left ventricular function and quality of life in heart failure due to Chagas disease. Trop Med Int Health 2017; 22:1314-1321. [PMID: 28805026 DOI: 10.1111/tmi.12939] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To evaluate the correlation of the total distance walked during the six-minute walk test (6MWT) with left ventricular function and quality of life in patients with Chagas Disease (ChD) complicated by heart failure. METHODS This is a cross-sectional study of adult patients with ChD and heart failure diagnosed based on Framingham criteria. 6MWT was performed following international guidelines. New York Heart Association functional class, brain natriuretic peptide (BNP) serum levels, echocardiographic parameters and quality of life (SF-36 and MLHFQ questionnaires) were determined and their correlation with the distance covered at the 6MWT was tested. RESULTS Forty adult patients (19 male; 60 ± 12 years old) with ChD and heart failure were included in this study. The mean left ventricular ejection fraction was 35 ± 12%. Only two patients (5%) ceased walking before 6 min had elapsed. There were no cardiac events during the test. The average distance covered was 337 ± 105 metres. The distance covered presented a negative correlation with BNP (r = -0.37; P = 0.02), MLHFQ quality-of-life score (r = -0.54; P = 0.002), pulmonary artery systolic pressure (r = -0.42; P = 0.02) and the degree of diastolic dysfunction (r = -0.36; P = 0.03) and mitral regurgitation (r = -0.53; P = 0.0006) and positive correlation with several domains of the SF-36 questionnaire. CONCLUSIONS The distance walked during the 6MWT correlates with BNP, quality of life and parameters of left ventricular diastolic function in ChD patients with heart failure. We propose this test to be adopted in endemic areas with limited resources to aid in the identification of patients who need referral for tertiary centres for further evaluation and treatment.
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Affiliation(s)
- Mayara C Chambela
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Mauro F F Mediano
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Roberto R Ferreira
- Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Rio de Janeiro, Brazil
| | - André M Japiassú
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Mariana C Waghabi
- Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Rio de Janeiro, Brazil
| | - Gilberto M S da Silva
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Roberto M Saraiva
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
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45
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Chagas Disease in the Mediterranean Area. CURRENT TROPICAL MEDICINE REPORTS 2017. [DOI: 10.1007/s40475-017-0123-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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46
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PANTI-MAY JA, DE ANDRADE RRC, GURUBEL-GONZÁLEZ Y, PALOMO-ARJONA E, SODÁ-TAMAYO L, MEZA-SULÚ J, RAMÍREZ-SIERRA M, DUMONTEIL E, VIDAL-MARTÍNEZ VM, MACHAÍN-WILLIAMS C, DE OLIVEIRA D, REIS MG, TORRES-CASTRO MA, ROBLES MR, HERNÁNDEZ-BETANCOURT SF, COSTA F. A survey of zoonotic pathogens carried by house mouse and black rat populations in Yucatan, Mexico. Epidemiol Infect 2017; 145:2287-2295. [PMID: 28689507 PMCID: PMC6231242 DOI: 10.1017/s0950268817001352] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 05/15/2017] [Accepted: 06/07/2017] [Indexed: 12/13/2022] Open
Abstract
The house mouse (Mus musculus) and the black rat (Rattus rattus) are reservoir hosts for zoonotic pathogens, several of which cause neglected tropical diseases (NTDs). Studies of the prevalence of these NTD-causing zoonotic pathogens, in house mice and black rats from tropical residential areas are scarce. Three hundred and two house mice and 161 black rats were trapped in 2013 from two urban neighbourhoods and a rural village in Yucatan, Mexico, and subsequently tested for Trypanosoma cruzi, Hymenolepis diminuta and Leptospira interrogans. Using the polymerase chain reaction we detected T. cruzi DNA in the hearts of 4·9% (8/165) and 6·2% (7/113) of house mice and black rats, respectively. We applied the sedimentation technique to detect eggs of H. diminuta in 0·5% (1/182) and 14·2% (15/106) of house mice and black rats, respectively. Through the immunofluorescent imprint method, L. interrogans was identified in 0·9% (1/106) of rat kidney impressions. Our results suggest that the black rat could be an important reservoir for T. cruzi and H. diminuta in the studied sites. Further studies examining seasonal and geographical patterns could increase our knowledge on the epidemiology of these pathogens in Mexico and the risk to public health posed by rodents.
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Affiliation(s)
- J. A. PANTI-MAY
- Doctorado en Ciencias Agropecuarias, Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, Merida, Mexico
| | - R. R. C. DE ANDRADE
- Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, Brasil
| | - Y. GURUBEL-GONZÁLEZ
- Departamento de Zoología, Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, Merida, Mexico
| | - E. PALOMO-ARJONA
- Departamento de Zoología, Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, Merida, Mexico
| | - L. SODÁ-TAMAYO
- Departamento de Zoología, Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, Merida, Mexico
| | - J. MEZA-SULÚ
- Departamento de Zoología, Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, Merida, Mexico
| | - M. RAMÍREZ-SIERRA
- Laboratorio de Parasitología, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Merida, Mexico
| | - E. DUMONTEIL
- Laboratorio de Parasitología, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Merida, Mexico
- Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
| | - V. M. VIDAL-MARTÍNEZ
- Laboratorio de Patología Acuática, Departamento de Recursos del Mar, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Merida, Merida, Mexico
| | - C. MACHAÍN-WILLIAMS
- Laboratorio de Arbovirología, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Merida, Mexico
| | - D. DE OLIVEIRA
- Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, Brasil
| | - M. G. REIS
- Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, Brasil
| | - M. A. TORRES-CASTRO
- Laboratorio de Enfermedades Emergentes y Re-emergentes, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Merida, Mexico
| | - M. R. ROBLES
- Centro de Estudios Parasitológicos y de Vectores, CONICET-Universidad Nacional de La Plata, La Plata, Argentina
| | - S. F. HERNÁNDEZ-BETANCOURT
- Departamento de Zoología, Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, Merida, Mexico
| | - F. COSTA
- Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Saúde, Salvador, Brasil
- Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brasil
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Flores A, Vitek C, Feria-Arroyo TP, Fredensborg BL. Temporal Variation in the Abundance and Timing of Daily Activity of Chagas Disease Vector Triatoma gerstaeckeri (Stål, 1859) in a Natural Habitat in the Lower Rio Grande Valley, South Texas. J Parasitol 2017; 103:574-578. [PMID: 28530845 DOI: 10.1645/17-50] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Chagas disease caused by Trypanosoma cruzi is a burden to millions of people in South and Central America. A sylvatic life cycle of the parasite exists in the Southern United States, but recent studies indicate an active peri-domestic life cycle of T. cruzi in Texas. The United States-Mexico border region in Texas displays areas of high poverty and sub-standard housing conditions which are important risk factors for a potential spill-over transmission to a domestic life cycle including humans. The objectives of the study were to examine short- and long-term temporal variation in vector activity and to evaluate the effect of different combinations of attractants on the capture of potential triatomine vectors. We collected local triatomine vectors (all of them identified as Triatoma gerstaeckeri) from a natural habitat in South Texas during the course of a year. The exact time of collection was recorded to examine the timing of flight activity of the triatomine vector. We also conducted a comparative study of the efficiency of 2 commonly used attractants (light and CO2) and the combination of those on the capture rate of Tr. gerstaeckeri. Our study indicates a short season of dispersal of Tr. gerstaeckeri (April/May) and it suggests a unimodal distribution of activity peaking between 2 and 3 hr after sunset. Ultra-violet light served as the main attractant of Tr. gerstaeckeri while CO2 from dry ice did not significantly contribute to the collection of vectors. The pronounced timing of activity in Tr. gerstaeckeri reported in this study contributes to our understanding of the epidemiology of T. cruzi in wildlife and its potential as a Chagas disease vector to humans in the Rio Grande Valley, South Texas.
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Affiliation(s)
- A Flores
- Department of Biology, The University of Texas Rio Grande Valley, 1201 W University Drive, Edinburg, Texas 78539
| | - C Vitek
- Department of Biology, The University of Texas Rio Grande Valley, 1201 W University Drive, Edinburg, Texas 78539
| | - T P Feria-Arroyo
- Department of Biology, The University of Texas Rio Grande Valley, 1201 W University Drive, Edinburg, Texas 78539
| | - B L Fredensborg
- Department of Biology, The University of Texas Rio Grande Valley, 1201 W University Drive, Edinburg, Texas 78539
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Dumonteil E, Herrera C. Ten years of Chagas disease research: Looking back to achievements, looking ahead to challenges. PLoS Negl Trop Dis 2017; 11:e0005422. [PMID: 28426735 PMCID: PMC5398480 DOI: 10.1371/journal.pntd.0005422] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Affiliation(s)
- Eric Dumonteil
- Department of Tropical Medicine, Vector-Borne Infectious Disease Research Center, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America
- * E-mail:
| | - Claudia Herrera
- Department of Tropical Medicine, Vector-Borne Infectious Disease Research Center, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America
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49
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Kollipara R, Peranteau AJ, Nawas ZY, Tong Y, Woc-Colburn L, Yan AC, Lupi O, Tyring SK. Emerging infectious diseases with cutaneous manifestations: Fungal, helminthic, protozoan and ectoparasitic infections. J Am Acad Dermatol 2017; 75:19-30. [PMID: 27317513 DOI: 10.1016/j.jaad.2016.04.032] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Revised: 04/11/2016] [Accepted: 04/12/2016] [Indexed: 12/27/2022]
Abstract
Given increased international travel, immigration, changing climate conditions, and the increased incidence of iatrogenic immunosuppression, fungal, protozoan, helminthic, and ectoparasitic infections that were once uncommon are being seeing more frequently in the Western hemisphere. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. In addition, delays in the diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. We review the epidemiology, cutaneous manifestations, diagnostic modalities, and treatment options for emerging fungal, protozoan, helminthic, and ectoparasitic infections. It should be noted, however, that throughout this review we cite statistics documenting their increased incidence to back-up these infections as emerging, and although some of the diagnoses are clinical, others rely on newer laboratory tests, and the possibility exists that the increased incidence could be caused by better detection methods.
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Affiliation(s)
- Ramya Kollipara
- Department of Dermatology, Texas Tech Health Sciences Center, Lubbock, Texas
| | | | | | - Yun Tong
- Center for Clinical Studies, Houston, Texas
| | - Laila Woc-Colburn
- Section of Infectious Diseases, Department of Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas
| | - Albert C Yan
- Section of Dermatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Omar Lupi
- Federal University of the State of Rio de Janeiro and Policlinica Geral do Rio de Janeiro, Rio de Janerio, Brazil
| | - Stephen K Tyring
- Center for Clinical Studies, Houston, Texas; Department of Dermatology, University of Texas Health Science Center, Houston, Texas
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50
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Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain. Antimicrob Agents Chemother 2017; 61:AAC.02098-16. [PMID: 28167559 DOI: 10.1128/aac.02098-16] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 01/22/2017] [Indexed: 11/20/2022] Open
Abstract
Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite Trypanosoma cruzi The current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for the biosynthesis of sterols in eukaryotes and the major target of clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoon-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain of T. cruzi The effects of different treatment regimens and drug delivery vehicles were evaluated in animals of both genders, with benznidazole serving as the reference drug. Regardless of the treatment scheme or delivery vehicle, VFV was more potent in both genders, causing a >99.7% peak parasitemia reduction, while the VNI values varied from 91 to 100%. Treatments with VNI and VFV resulted in 100% animal survival and 0% natural relapse after the end of therapy, though, except for the 120-day treatment schemes with VFV, relapses after three cycles of immunosuppression were observed in each animal group, and quantitative PCR analysis revealed a very light parasite load in the blood samples (sometimes below or near the detection limit, which was 1.5 parasite equivalents/ml). Our studies support further investigations of this class of compounds, including their testing against other T. cruzi strains and in combination with other drugs.
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