Target product profile for a test for the early assessment of treatment efficacy in chagas disease patients: An expert consensus

• Autores: Alonso Padilla, Julio; Abril, Marcelo; Alarcón de Noya, Belkisyolé; Almeida, Igor C.; Angheben, Andrea; Araujo Jorge, Tania; Chatelain, Eric; Esteva, Mónica Inés; Gascón, Joaquim; Grijalva, Mario J.; Guhl, Felipe; Hasslocher Moreno, Alejandro Marcel; López, Manuel Carlos; Luquetti, Alejandro; Noya, Oscar; Pinazo, María Jesús; Ramsey, Janine M.; Ribeiro, Isabela; Ruiz, Andres Mariano; Schijman, Alejandro Gabriel; Sosa-Estani, Sergio Alejandro; Thomas Carazo, María del Carmen; Torrico, Faustino; Zreinid, Maan; Picado, Albert
• Año de publicación: 2020
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Chagas disease; Biomarkers
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

The absence of a test for the early assessment of treatment efficacy, often called atest of cure (ToC), is a major obstacle to Chagas disease control. Accurately monitoring treatment response would undoubtedly improve patient management and support the conduct of clinical trials. Although treatment efficacy and treatment response may be conceptually different, we are using these terms synonymously for the purpose of the current target product profile(TPP).Unfortunately, there is no gold-standard test for the early determination of whether someone who has been treated for chronic Chagas disease has been cured or not. Current methods used for monitoring Chagas disease treatment efficacy are suboptimal due to the fact that: (1) clinical progression of the disease is silent and associated with complex and mostly unknown host?pathogen interactions; (2) once in the chronic stage, infected subjects remain seropositive for years, with very low and intermittent parasitemia counts; and (3) as a consequence, in the chronic phase, parasitological detection methods have very low sensitivity, whereas molecular detection can only be done in reference laboratories. Besides, clinical evaluation may not be specific to Chagas disease and cannot be used in cases where some structural tissue damagealready exists. In addition, measuring seroconversion by conventional tests is not viable as it may take years or decades for a patient with chronic disease to revert serologically. Finally, the posttreatment detection of circulating parasites (through their DNA) by molecular amplification techniques, such as quantitative polymerase chain reaction (qPCR), may be useful for determining treatment failure, but a negative qPCR result cannot be considered a surrogate of cure.Development of a test that can determine in a timely manner if a patient treated for Chagas disease has successfully responded to treatment has therefore been identified as a priority.As mentioned above, such a test could be used in two different scenarios or use cases: (1) the daily clinical management (DCM) of Chagas disease patients posttreatment to decide if and/or when a patient should be followed up after treatment completion and (2) in the context of clinical trials (CT), where the test would be used as the endpoint measurement for the evaluation of new anti?T. cruzi treatments.The development of this test (or tests) should be guided by a TPP. TPPs for a test to assess treatment response in Chagas disease patients have been suggested previously. Building on them, we now present a TPP specifically describing the required technical and performance characteristics of a test to determine if a Chagas disease patient has been cured posttreatment. We have considered two use scenarios: day-to-day healthcare provision and clinical evaluation of new anti?T. cruzi drugs or alternative regimens of the drugs currently available.
Fil: Alonso Padilla, Julio. Universidad de Barcelona; España
Fil: Abril, Marcelo. Fundación Mundo Sano; Argentina
Fil: Alarcón de Noya, Belkisyolé. Universidad Central de Venezuela; Venezuela
Fil: Almeida, Igor C.. University of Texas at El Paso; Estados Unidos
Fil: Angheben, Andrea. Universita di Verona; Italia
Fil: Araujo Jorge, Tania. Instituto Oswaldo Cruz; Brasil
Fil: Chatelain, Eric. Drugs For Neglected Diseases Initiative; Brasil
Fil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina
Fil: Gascón, Joaquim. Universidad de Barcelona; España
Fil: Grijalva, Mario J.. Ohio University; Estados Unidos
Fil: Guhl, Felipe. Universidad de Los Andes; Venezuela
Fil: Hasslocher Moreno, Alejandro Marcel. Instituto Oswaldo Cruz; Brasil
Fil: López, Manuel Carlos. Consejo Superior de Investigaciones Científicas; España
Fil: Luquetti, Alejandro. No especifíca;
Fil: Noya, Oscar. Universidad Central de Venezuela; Venezuela
Fil: Pinazo, María Jesús. Universidad de Barcelona; España
Fil: Ramsey, Janine M.. Instituto Nacional de Salud Pública; México
Fil: Ribeiro, Isabela. No especifíca;
Fil: Ruiz, Andres Mariano. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C.G. Malbrán". Instituto Nacional de Parasitología "Dr. M. Fatala Chabén"; Argentina
Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina
Fil: Thomas Carazo, María del Carmen. Consejo Superior de Investigaciones Científicas; España
Fil: Torrico, Faustino. Universidad Mayor de San Simón; Bolivia
Fil: Zreinid, Maan. No especifíca;
Fil: Picado, Albert. No especifíca;