Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity

Abstract

This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape.

2 nd Brazilian Consensus on Chagas Disease, 2015

“…João Carlos Pinto Dias [1] , Alberto Novaes Ramos Jr [2] , Eliane Dias Gontijo [3] , Alejandro Luquetti [4] , Maria Aparecida Shikanai-Yasuda [5] , José Rodrigues Coura [6] , Rosália Morais Torres [3] , José Renan da Cunha Melo [3] , Eros Antonio de Almeida [7] , Wilson de Oliveira Junior [8] , Antônio Carlos Silveira [9] , Joffre Marcondes de Rezende [10] , Fabiane Scalabrini Pinto [11] , Antonio Walter Ferreira [12] , Anis Rassi [13] , Abílio Augusto Fragata Filho [14] , Andréa Silvestre de Sousa [15] , Dalmo Correia [16] , Ana Maria Jansen [6] , Glaucia Manzan Queiroz Andrade [3] , Constança Felícia De Paoli de Carvalho Britto [6] , Ana Yecê das Neves Pinto [17] , Anis Rassi Junior [13] , Dayse Elisabeth Campos [18] , Fernando Abad-Franch [1] , Silvana Eloi Santos [3] , Egler Chiari [19] , Alejandro Marcel Hasslocher-Moreno [15] , Eliane Furtado Moreira [20] , Divina Seila de Oliveira Marques [21] , Eliane Lages Silva [22] , José Antonio Marin-Neto [23] , Lúcia Maria da Cunha Galvão [19] , Sergio Salles Xavier [24] , Sebastião Aldo da Silva Valente [17] , Noêmia Barbosa Carvalho [25] , Alessandra Viana Cardoso [26] , Rafaella Albuquerque e Silva [26] , Veruska Maia da Costa [26] , Simone Monzani Vivaldini …”

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

“…As an example, it has been recommended to take the T. cruzi near-clades ('DTUs') as a basis for all studies dealing with drug research concerning this parasite (Zingales et al, 2014).…”

Antiprotozoal Activity of Extracts of Elaeodendron Trichotomum (Celastraceae)

“…The impact of Chagas disease on annual productivity in Latin America has been estimated in US$ 1.2 billion. The acute phase of this disease may not shows clinical manifestations but may progresses to a chronic phase, in which the patients may suffer cardiomyopathy, digestive megasyndrome or both ( Zingales et al, 2014).…”