Coinfection by multiple Trypanosoma cruzi clones: a new perspective on host-parasite relationship with consequences for pathogenesis and management of Chagas disease.

SUMMARYChagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi (Tc), infecting 6-7 million people. It is transmitted by insect vectors, orally, through infected tissues, or congenitally. Tc infection can progress toward chronic cardiac and/or digestive severe and fatal CD in 20%-40% of patients. Tc exhibits an important genetic and phenotypic intraspecies diversity and a preponderant clonal population structure. The impact of multiclonal coinfections has been little studied in CD patients. Relationships between the currently used discrete typing unit (DTU)-based classification of Tc lineages and the occurrence of the different clinical forms of CD, its congenital transmission, as well as the efficacy of trypanocidal molecules (benznidazole and nifurtimox) could not be established. In this review, we revisit the different aspects of Tc diversity and analyze the impact of infections with multiple clones and their variants on the dynamic and pathogenesis of CD and its maternal-fetal transmission. We propose to call "cruziome" all the Tc clones and their variants infecting a given host and provide strong evidence that (i) multiclonal Tc infections are likely the rule rather than the exception; (ii) each "cruziome" is associated with a unique combination of virulence factors, tissular tropisms, and host immune responses; (iii) accordingly, some particularly harmful "cruziomes" likely trigger the occurrence and progression of CD and might also favor the congenital transmission of parasites. We propose that our concept of "cruziome" should be taken into consideration because of its practical consequences in epidemiological studies, laboratory diagnosis, clinical management, and treatment of CD.