Trypanosoma cruzi genetic diversity associates with serological diagnostic assay performance

Background Infections with Trypanosoma cruzi can lead to Chagas disease. Diagnosis principally relies on serological assays, although there is no gold standard assay, and discordant results among tests are increasingly reported. Parasite diversity has been proposed as a potential factor underlying variable diagnostic performance, but clear associations have not been detected yet. Therefore, we tested here how parasite strain composition in infected hosts -the “cruziome”- may associate with serological outcomes in this cohort. Methods Archived blood samples from patients from Argentina, Honduras and Mexico were stratified as confirmed positive or serodiscordant based on previous serological testing, and T. cruzi parasites were successfully genotyped in 73 patients. Results A total of 532 mini-exon sequences were obtained (7.3 ± 0.5 haplotypes/individual), covering TcI, TcII, TcIV, TcV and TcVI DTUs, in similar proportions among countries, but variable proportions among individuals. Phylogenetic analysis indicated a significant geographic structuring of TcI, TcII, TcV and TcVI among countries, as well as clustering associated with discordant serology for TcI, TcII and TcV DTUs. Between 5–12 SNPs among these DTUs supported the association with discordant serology, and their frequency among countries mirrored that of serodiscordance. Conclusion These results point to the cruziome and genetic differentiation within TcI, TcII and TcV DTUs to explain a large part of geographic differences in diagnostic performance. Thus, it is critical to account for the local diversity of T. cruzi strains throughout the continent for the development of improved diagnosis.