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A GUIDE FOR THE GENERATION OF REPOSITORIES OF CLINICAL SAMPLES FOR RESEARCH ON CHAGAS DISEASE
Blood
Diagnostic medicine
Parasitic diseases
Biomarkers
Antiparasitic therapy
Specimen storage
Urine
Produção científica do Laboratório de Inovações em Terapias, Ensino e Bioprodutos.
Author summary: The diagnosis of Chagas disease requires costly equipment and trained personnel, which unavailability hinders access to diagnosis, and treatment, in vast areas of endemic regions. Additionally, timely assessment of treatment efficacy is complicated due to the slow reversion of serological anti-T. cruzi reactivity. Hence, there is an urgent need for biomarkers of early therapeutic efficacy and disease prognosis, as well as more practical diagnostic tools. To conduct studies that can address these needs, it is essential to have collections of clinical samples with good quality, traceability, and appropriately associated clinical-epidemiological information. In this work, we provide a standard protocol to collect, process, store, and transport clinical samples from Chagas disease patients. The manual was produced upon reaching a consensus among the experts within the NHEPACHA network, a coalition of clinical and academic researchers from the Americas and Spain that pursues the identification and validation of new biomarkers and diagnostics for Chagas disease.
Author
Martínez-Peinado, Nieves
Gabaldón-Figueira, Juan Carlos
Ferreira, Roberto Rodrigues
Carmen Thomas, María
Carlos López, Manuel
Araujo-Jorge, Tania Cremonini de
Noya, Belkisyolé Alarcón de
Berón, Soledad
Ramsey, Janine
Losada Galván, Irene
Gabriel Schijman, Alejandro
González Martínez, Adriana
Mariano Ruiz, Andrés
Rojas, Gimena
Saraiva, Roberto Magalhães
Noya-González, Oscar
Gómez, Andrea
Maldonado, Rosa A.
Pinto, Jimmy
Torrico, Faustino
Scandale, Ivan
Agüero, Fernán
Pinazo, María-Jesús
Gascón, Joaquim
Hasslocher-Moreno, Alejandro Marcel
Alonso-Padilla, Julio
Gabaldón-Figueira, Juan Carlos
Ferreira, Roberto Rodrigues
Carmen Thomas, María
Carlos López, Manuel
Araujo-Jorge, Tania Cremonini de
Noya, Belkisyolé Alarcón de
Berón, Soledad
Ramsey, Janine
Losada Galván, Irene
Gabriel Schijman, Alejandro
González Martínez, Adriana
Mariano Ruiz, Andrés
Rojas, Gimena
Saraiva, Roberto Magalhães
Noya-González, Oscar
Gómez, Andrea
Maldonado, Rosa A.
Pinto, Jimmy
Torrico, Faustino
Scandale, Ivan
Agüero, Fernán
Pinazo, María-Jesús
Gascón, Joaquim
Hasslocher-Moreno, Alejandro Marcel
Alonso-Padilla, Julio
Affilliation
University of Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain / Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació. Departament de Biologia, Sanitat i Medi Ambient. Secció de Parasitologia. Barcelona, Spain.
University of Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Aplicada e Bioinovações. Rio de Janeiro, RJ, Brasil.
Parque Tecnológico de la Salud de Granada. Consejo Superior de Investigaciones Científicas. Instituto de Parasitología y Biomedicina López Neyra. Granada, Spain.
Parque Tecnológico de la Salud de Granada. Consejo Superior de Investigaciones Científicas. Instituto de Parasitología y Biomedicina López Neyra. Granada, Spain.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Universidad Central de Venezuela. Facultad de Medicina. Instituto de Medicina Tropical. Caracas, Venezuela.
Fundación Mundo Sano. Buenos Aires, Argentina.
Instituto Nacional de Salud Pública. Centro Regional de Investigación en Salud Pública. Tapachula, Chiapas, México.
University of Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain / Hospital Universitario 12 de Octubre. Madrid, Spain.
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Laboratorio de Biología Molecular de la Enfermedad de Chagas. Buenos Aires, Argentina.
Salvando Latidos A. C. Departamento de Investigación. Guadalajara, Mexico / Instituto Cardiovascular de Mínima Invasión. Departamento de Investigación. Guadalajara, Mexico.
Ministerio de Salud. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben" ANLIS MALBRÁN. Buenos Aires, Argentina / Consejo Nacional de Investigaciones Científicas y Técnicas. Buenos Aires, Argentina.
Universidad Mayor de San Simón and Fundación CEADES. Cochabamba, Bolivia.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doença de Chagas. Rio de Janeiro, RJ, Brasil.
Universidad Central de Venezuela. Facultad de Medicina. Instituto de Medicina Tropical. Caracas, Venezuela / Universidad Central de Venezuela. Facultad de Medicina. Escuela "Luís Razetti". Cátedra de Parasitología. Caracas, Venezuela / Ministerio del Poder Popular para la Salud. Instituto de Altos Estudios "Dr. Arnoldo Gabaldón". Centro para Estudios Sobre Malaria. Caracas, Venezuela.
Fundación Mundo Sano. Buenos Aires, Argentina.
The University of Texas at El Paso. Department of Biological Sciences. El Paso, TX, USA.
Universidad Mayor de San Simón and Fundación CEADES. Cochabamba, Bolivia.
Universidad Mayor de San Simón and Fundación CEADES. Cochabamba, Bolivia.
Drugs for Neglected Diseases Initiative. Geneva, Switzerland.
Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biotecnológicas. San Martín, Buenos Aires, Argentina / Universidad de San Martín. Escuela de Bio y Nanotecnologías. San Martín, Buenos Aires, Argentina.
Drugs for Neglected Diseases Initiative. Geneva, Switzerland / Instituto de Salud Carlos III. CIBER de Enfermedades Infecciosas. Madrid, Spain.
University of Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain / Instituto de Salud Carlos III. CIBER de Enfermedades Infecciosas. Madrid, Spain.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doença de Chagas. Rio de Janeiro, RJ, Brasil.
University of Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain / Instituto de Salud Carlos III. CIBER de Enfermedades Infecciosas. Madrid, Spain.
University of Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Aplicada e Bioinovações. Rio de Janeiro, RJ, Brasil.
Parque Tecnológico de la Salud de Granada. Consejo Superior de Investigaciones Científicas. Instituto de Parasitología y Biomedicina López Neyra. Granada, Spain.
Parque Tecnológico de la Salud de Granada. Consejo Superior de Investigaciones Científicas. Instituto de Parasitología y Biomedicina López Neyra. Granada, Spain.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Universidad Central de Venezuela. Facultad de Medicina. Instituto de Medicina Tropical. Caracas, Venezuela.
Fundación Mundo Sano. Buenos Aires, Argentina.
Instituto Nacional de Salud Pública. Centro Regional de Investigación en Salud Pública. Tapachula, Chiapas, México.
University of Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain / Hospital Universitario 12 de Octubre. Madrid, Spain.
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Laboratorio de Biología Molecular de la Enfermedad de Chagas. Buenos Aires, Argentina.
Salvando Latidos A. C. Departamento de Investigación. Guadalajara, Mexico / Instituto Cardiovascular de Mínima Invasión. Departamento de Investigación. Guadalajara, Mexico.
Ministerio de Salud. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben" ANLIS MALBRÁN. Buenos Aires, Argentina / Consejo Nacional de Investigaciones Científicas y Técnicas. Buenos Aires, Argentina.
Universidad Mayor de San Simón and Fundación CEADES. Cochabamba, Bolivia.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doença de Chagas. Rio de Janeiro, RJ, Brasil.
Universidad Central de Venezuela. Facultad de Medicina. Instituto de Medicina Tropical. Caracas, Venezuela / Universidad Central de Venezuela. Facultad de Medicina. Escuela "Luís Razetti". Cátedra de Parasitología. Caracas, Venezuela / Ministerio del Poder Popular para la Salud. Instituto de Altos Estudios "Dr. Arnoldo Gabaldón". Centro para Estudios Sobre Malaria. Caracas, Venezuela.
Fundación Mundo Sano. Buenos Aires, Argentina.
The University of Texas at El Paso. Department of Biological Sciences. El Paso, TX, USA.
Universidad Mayor de San Simón and Fundación CEADES. Cochabamba, Bolivia.
Universidad Mayor de San Simón and Fundación CEADES. Cochabamba, Bolivia.
Drugs for Neglected Diseases Initiative. Geneva, Switzerland.
Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biotecnológicas. San Martín, Buenos Aires, Argentina / Universidad de San Martín. Escuela de Bio y Nanotecnologías. San Martín, Buenos Aires, Argentina.
Drugs for Neglected Diseases Initiative. Geneva, Switzerland / Instituto de Salud Carlos III. CIBER de Enfermedades Infecciosas. Madrid, Spain.
University of Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain / Instituto de Salud Carlos III. CIBER de Enfermedades Infecciosas. Madrid, Spain.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doença de Chagas. Rio de Janeiro, RJ, Brasil.
University of Barcelona. Hospital Clínic. Barcelona Institute for Global Health. Barcelona, Spain / Instituto de Salud Carlos III. CIBER de Enfermedades Infecciosas. Madrid, Spain.
Abstract
Chagas disease, caused by the parasite Trypanosoma cruzi, affects over 6 million people, mainly in Latin America. Two different clinical phases, acute and chronic, are recognised. Currently, 2 anti-parasitic drugs are available to treat the disease (nifurtimox and benznidazole), but diagnostic methods require of a relatively complex infrastructure and trained personnel, limiting its widespread use in endemic areas, and the access of patients to treatment. New diagnostic methods, such as rapid tests (RDTs) to diagnose chronic Chagas disease, or loop-mediated isothermal amplification (LAMP), to detect acute infections, represent valuable alternatives, but the parasite’s remarkable genetic diversity might make its implementation difficult. Furthermore, determining the efficacy of Chagas disease treatment is complicated, given the slow reversion of serological anti-T. cruzi antibody reactivity, which may even take decades to occur. New biomarkers to evaluate early therapeutic efficacy, as well as diagnostic tests able to detect the wide variety of circulating genotypes, are therefore, urgently required. To carry out studies that address these needs, high-quality and traceable samples from T. cruzi-infected individuals with different geographical backgrounds, along with associated clinical and epidemiological data, are necessary. This work describes the framework for the creation of such repositories, following standardised and uniform protocols, and considering the ethical, technical, and logistic aspects of the process. The manual can be adapted according to the resources of each laboratory, to guarantee that samples are obtained in a reproducible way, favouring the exchange of data among different work groups, and their generalizable evaluation and analysis. The main objective of this is to accelerate the development of new diagnostic methods and the identification of biomarkers for Chagas disease.
Keywords
Chagas diseaseBlood
Diagnostic medicine
Parasitic diseases
Biomarkers
Antiparasitic therapy
Specimen storage
Urine
Publisher
Public Library of Science
Citation
MARTÍNEZ-PEINADO, Nieves et al. A guide for the generation of repositories of clinical samples for research on Chagas disease. PLoS Neglected Tropical Diseases, v. 18, n. 8, p. 1-13, 15 Aug. 2024.DOI
10.1371/journal.pntd.0012166ISSN
1935-2727Notes
Produção científica do Laboratório de Genômica Aplicada e Bioinovações.Produção científica do Laboratório de Inovações em Terapias, Ensino e Bioprodutos.
Author summary: The diagnosis of Chagas disease requires costly equipment and trained personnel, which unavailability hinders access to diagnosis, and treatment, in vast areas of endemic regions. Additionally, timely assessment of treatment efficacy is complicated due to the slow reversion of serological anti-T. cruzi reactivity. Hence, there is an urgent need for biomarkers of early therapeutic efficacy and disease prognosis, as well as more practical diagnostic tools. To conduct studies that can address these needs, it is essential to have collections of clinical samples with good quality, traceability, and appropriately associated clinical-epidemiological information. In this work, we provide a standard protocol to collect, process, store, and transport clinical samples from Chagas disease patients. The manual was produced upon reaching a consensus among the experts within the NHEPACHA network, a coalition of clinical and academic researchers from the Americas and Spain that pursues the identification and validation of new biomarkers and diagnostics for Chagas disease.
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