Chagas Disease and other Emergent and Re-Emergent Diseases

With more than 6 million people infected with the protozoan Trypanosoma cruzi and 75 million at risk, Chagas remains a largely neglected disease. Less than 1% of those affected have access to treatment. The main routes of transmission are vector-borne (through the bite of a triatomine insect known as the bedbug, vinchuca or other names in different endemic countries), followed by vertical transmission (from mother to child) and oral transmission (through ingestion of food or drink contaminated with the parasite). It can also occur through blood transfusions, organ donations or laboratory accidents.

Although endemic to Latin America, where the vector is found in rural areas, expansion, climatic and social changes and migration have made it a global public health concern. For this reason, we work in endemic areas with high incidence, such as Bolivia and Paraguay.

All of our research lines aim to strengthen comprehensive care and the capacity of health systems to respond to Chagas disease. They have a community-based approach and are linked to information, education and communication (IEC) activities. The main objectives are Improved knowledge of the pathophysiological mechanisms in the host-parasite interaction; More accessible diagnostics, such as the Loop-Mediated Isothermal Amplification (LAMP) method for the detection of Chagas' disease.

Strategic alliances

We work with a wide network of national and international allies and partners from the public, private and academic sectors. In Bolivia, with Fundación SANIT; Fundación CEADES; Universidad Autónoma Gabriel René Moreno. In Paraguay, with Fundación CEDIC, Fundación CIRD and the Paraguayan Ministry of Health through the National Malaria Eradication Service (SENEPA). In Argentina, the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). In the United States, the University of Texas-El Paso (UTEP). In Spain, the Instituto de Parasitología y Biomedicina López-Neyra (IPBLN). Also the Spanish Agency for International Development Cooperation (AECID) and the New Drug Development Initiative (DND)i; the Novartis Global Health Division and the PROBITAS Foundation.

We are aligned with the PAHO-WHO goals for the elimination of this disease and are founding members of the Global Chagas Coalition and the Nhepacha Research Network, as well as being part of the SEMTSI NTDs group. We coordinate the Consolidated Research Group (GRC) "GREPIMER - Grup de Recerca en Patologia Importada i Malalties Emergents i Reemergents".

Goals

• To generate valuable knowledge on the physiopathology of T. cruzi infection, in order to understand its interactions with its human and animal hosts and/or vectors.
• To identify, validate and develop new diagnostic methods, biomarkers of therapeutic efficacy and for the prognosis of patients affected by Chagas disease and its possible complications such as cardiologic symptomatology.
• To find and develop new drugs against T. cruzi, including the clinical evaluation of new therapeutic schemes.
• To foster capacity strengthening of the health system, training personnel and developing research capacities regarding Chagas in Bolivia and Paraguay, as well as promoting translation of research results into impact.

Main lines of research

• Identification of compounds with anti-Trypanosoma cruzi activity.
• Biomarkers of therapeutic efficacy and biomarkers for early detection of cardiac damage in patients with Chagas disease.
• Implementation and validation of alternative diagnostics for the detection of chronic and acute T. cruzi infection.
• Clinical trials of new drugs for the treatment of Chagas disease.
• Strategies to increase accessibility to diagnosis and treatment.
• Community involvement.
• Epidemiology of Chagas disease and Leishmaniasis.

Ongoing projects

• “New chemotherapy regimens and biomarkers for Chagas disease - TESEO”. Research Proposal U01 2 AI19783-01A1. Funded by the National Institutes of Health (NIH), USA 
• “Fortalecimiento del Ministerio de Salud del Paraguay en la lucha Global contra la Enfermedad de Chagas mediante la conformación de una red de atención protocolizada de Centros del Sistema Nacional de Salud”. Funded by: AECID
• “Mejora del acceso a una atención integral a través del fortalecimiento del diagnóstico de Chagas y otras enfermedades prevalentes en el Departamento Presidente Hayes (Paraguay)”. Funded by Global Laboratory Initiative (GLI) – Fundación Probitas 
• RENATEC (Recursos Naturales para la enfermedad de chagas). (223RT0140) CYTED. Programa Iberoamericano de Ciencia y tecnología.
• “Insight on climate and social participatory research for integral management of vector-borne zoonosis caused by Trypanosoma cruzi and Leishmania spp. in the Bolivian Gran Chaco - CLIMSOCTRYPBOL”. Funded by EULAC.
• Chagas) in the Gran Chaco region of Tarija, Bolivia. 
• “Estudio de los procesos de inmunotrombosis y lipotoxicidad como mecanismos de patogénesis en la enfermedad de Chagas - ChagasPATH”. Funded by the Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Health; PI18/00238, FIS)
• Healthcare system strengthening for cardiovascular disease management (including Chagas) in the Gran Chaco region of Tarija, Bolivia.
• “Field validation of Trypanosoma cruzi-LAMP: a molecular point-of-care test for the control of congenital Chagas disease – ChagasLAMP”. (https://www.ghitfund.org/investment/portfoliodetail/detail/184/en). Funded by the Global Health Innovative Technology (GHIT).
• “Estudio de los procesos de inmunotrombosis y lipotoxicidad como mecanismos de patogénesis en la enfermedad de Chagas - ChagasPATH”. Funded by the Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Health; PI18/00238, FIS)

Past projects

• “Contribuir a la lucha global contra el Chagas mediante la adecuación del modelo protocolizado a las estructuras del SNS, conformando una red de atención (enfoque inclusivo), en Bolivia”. Convenio AECID, 14-CO1-558.
• Barcelona CaixaResearch Living Lab  
• Programa de intercambio de conocimiento entre Paraguay-Bolivia-España para optimizar el manejo de la enfermedad de Chagas en el contexto de la pandemia COVID19

Scientific publications

• Efficacy and safety of fexinidazole for treatment of chronic indeterminate Chagas disease (FEXI-12): a multicentre, randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2024 Jan. Pinazo MJ, Forsyth C, Losada I, Esteban ET, García-Rodríguez M, Villegas ML, Molina I, Crespillo-Andújar C, Gállego M, Ballart C, Ramirez JC, Aden T, Hoerauf A, Pfarr K, Vaillant M, Marques T, Fernandes J, Blum B, Ribeiro I, Sosa-Estani S, Barreira F, Gascón J; FEXI-12 Study Team. (DNDi-Fex-12-CH) funded by the Drugs for Neglected Diseases Initiative (DNDi); Role: collaborator (trial coordinator: J. Gascón). https://pubmed.ncbi.nlm.nih.gov/38218194/
• Characterization of Latin American migrants at risk for Trypanosoma cruzi infection in a non-endemic setting. Insights into initial evaluation of cardiac and digestive involvement. Laynez-Roldán P, Losada-Galván I, Posada E, de la Torre Ávila L, Casellas A, Sanz S, Subirà C, Rodriguez-Valero N, Camprubí-Ferrer D, Vera I, Roldán M, Aldasoro E, Oliveira-Souto I, Calvo-Cano A, Valls ME, Álvarez-Martínez MJ, Gállego M, Abras A, Ballart C, Muñoz J, Gascón J, Pinazo MJ. PLoS Negl Trop Dis 2023 Jul 13;17(7):e0011330. doi: 10.1371/journal.pntd.0011330. eCollection 2023 Jul. 
• Identification of compounds with activity against Trypanosoma cruzi within a collection of synthetic nucleoside analogs. Barnadas-Carceller B, Martinez-Peinado N, Gómez LC, Ros-Lucas A, Gabaldón-Figueira JC, Diaz-Mochon JJ, Gascon J, Molina IJ, Pineda de Las Infantas Y Villatoro MJ, Alonso-Padilla J. Front Cell Infect Microbiol. 2023 Jan 13;12:1067461. doi: 10.3389/fcimb.2022.1067461. 
• Results and evaluation of the expansion of a model of comprehensive care for Chagas disease within the National Health System: The Bolivian Chagas network. Pinazo MJ, Rojas-Cortez M, Saravia R, Garcia-Ruiloba W, Ramos C, Pinto Rocha JJ, Ortiz L, Castellon M, Mendoza-Claure N, Lozano D, Torrico F, Gascon J; Chagas Platform and Chagas Healthcare Network working group. PLoS Negl Trop Dis. 2022 Feb 17;16(2):e0010072
• Worldwide Control and Management of Chagas Disease in a New Era of Globalization: a Close Look at Congenital Trypanosoma cruzi Infection. Abras A, Ballart C, Fernández-Arévalo A, Pinazo MJ, Gascón J, Muñoz C, Gállego M. Clin Microbiol Rev. 2022 Apr 20;35(2):e0015221.
• The Use of AlphaFold for In Silico Exploration of Drug Targets in the Parasite Trypanosoma cruzi. Ros-Lucas A, Martinez-Peinado N, Bastida J, Gascón J, Alonso-Padilla J. Front Cell Infect Microbiol. 2022 Jul 14;12:944748.
• Anti-Trypanosoma cruzi activity of alkaloids isolated from Habranthus brachyandrus (Amaryllidaceae) from Argentina. Martinez-Peinado N, Ortiz JE, Cortes-Serra N, Pinazo MJ, Gascon J, Tapia A, Roitman G, Bastida J, Feresin GE, Alonso-Padilla J. Phytomedicine. 2022 Jul;101:154126. doi: 10.1016/j.phymed.2022.154126.
• New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial. Torrico F, Gascón J, Barreira F, Blum B, Almeida IC, Alonso-Vega C, Barboza T, Bilbe G, Correia E, Garcia W, Ortiz L, Parrado R, Ramirez JC, Ribeiro I, Strub-Wourgaft N, Vaillant M, Sosa-Estani S; BENDITA study group. Lancet Infect Dis. 2021 Aug;21(8):1129-1140.
• Target product profile for a test for the early assessment of treatment efficacy in Chagas disease patients: An expert consensus. Alonso-Padilla J, Abril M, Alarcón de Noya B, Almeida IC, Angheben A, Araujo Jorge T, Chatelain E, Esteva M, Gascón J, Grijalva MJ, Guhl F, Hasslocher-Moreno AM, López MC, Luquetti A, Noya O, Pinazo MJ, Ramsey JM, Ribeiro I, Ruiz AM, Schijman AG, Sosa-Estani S, Thomas MC, Torrico F, Zrein M, Picado A.PLoS Negl Trop Dis. 2020 Apr 23;14(4):e000803
• Use of rapid diagnostic tests (RDTs) for conclusive diagnosis of chronic Chagas disease - field implementation in the Bolivian Chaco region. Lozano D, Rojas L, Méndez S, Casellas A, Sanz S, Ortiz L, Pinazo MJ, Abril M, Gascón J, Torrico F, Alonso-Padilla J. PLoS Negl Trop Dis. 2019 Dec 19;13(12):e0007877.
• Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial. Torrico F, Gascon J, Ortiz L, Alonso-Vega C, Pinazo MJ, Schijman A, Almeida IC, Alves F, Strub-Wourgaft N, Ribeiro I; E1224 Study Group. Lancet Infect Dis. 2018 Apr;18(4):419-430.