Abstract
Chagas disease is an important vector-borne neglected tropical disease that causes great health and economic losses. The etiological agent, Trypanosoma cruzi, is a protozoan parasite endemic to the Americas, comprised by important diversity, which has been suggested to contribute to poor serological diagnostic performance. Current nomenclature describes seven discrete typing units (DTUs), or lineages. We performed the first large scale analysis of T. cruzi diversity among 52 previously published genomes from strains covering multiple countries and parasite DTUs and assessed how different markers summarize this genetic diversity. We also examined how seven antigens currently used in commercial serologic tests are conserved across this diversity of strains. DTU structuration was confirmed at the whole-genome level, with evidence of sub-DTU diversity, associated in part to geographic structuring. We observed very comparable phylogenetic tree topographies for most of the 32 markers investigated, with clear clustering of sequences by DTU, and a few of these markers suggested some degree of intra-lineage diversity. At least three of the currently used antigens represent poorly conserved sequences, with sequences used in tests quite divergent from sequences in many strains. Most markers are well suited for estimating parasite diversity to DTU level, and a few are particularly well-suited to assess intra-DTU diversity. Analysis of antigen sequences across all strains indicates that antigenic diversity is a likely explanation for limited diagnostic performance in Central and North America.
Highlights
Trypanosoma cruzi, the etiological agent of Chagas disease, is a protozoan parasite that infects a wide range of mammals
Using a representative subset of 13 genomes covering six discrete typing units (DTUs), we observed a clear clustering of strains according to their DTU (Figure 1A) confirming that T. cruzi DTU genetic structure is present at the whole genome level across all six DTUs
While this subdivision has been previously established with a small number of genetic markers [7], it is important to see it reflected at the whole genome level as this confirms that it corresponds to a strong evolutionary signal of T. cruzi genetic structure and strain diversity, and a useful classification of strains
Summary
Trypanosoma cruzi, the etiological agent of Chagas disease, is a protozoan parasite that infects a wide range of mammals. It is transmitted in the feces of insects of the subfamily Triatominae during blood-feeding, congenitally, or orally via contaminated food or drink. Thirty to forty percent of individuals who are infected with the parasite go on to develop chronic disease, marked by cardiomyopathies or gastrointestinal disorders such as megaesophagus or megacolon. The highest disease burden lies in Latin America and estimates suggest that around six million people may be infected globally [4]. With approximately 70 million persons at risk, Chagas disease costs 806,170 disability-adjusted life years (DALYs) annually, as well as about $627 million in patient care [5]
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