Parasite burden, genetic profiling and geographic distribution of Trypanosoma cruzi detected in chronic Chagas disease patients from Córdoba, Argentina.

Chagas disease (CD) exhibits marked clinical heterogeneity during its chronic phase, which has been partially attributed to the genetic diversity of Trypanosoma cruzi [which is currently classified into six Discrete Typing Units (DTUs, Tc I - Tc VI)]. However, establishing a direct genotype-phenotype correlation remains challenging. We conducted a cross-sectional study in 202 chronic CD patients from Córdoba, Argentina, combining molecular typing (mini-exon, 24Sα rRNA, 18S rRNA), quantitative PCR-based parasite load estimation, and clinical stratification according to cardiomyopathy presence and severity. The predominant DTU (n = 129) was Tc V (n = 90; 70 %), followed by Tc II (n = 35; 27 %) and Tc VI (n = 4; 3 %), consistent with regional transmission patterns. No significant association was observed between infecting DTU and the overall presence of cardiomyopathy. An association between Tc V and more severe cardiac involvement emerged in subgroup analyses, but it should be interpreted cautiously due to limited sample size. Circulating parasite load showed high inter-individual variability and was not significantly associated with sex, clinical group, or infecting DTU. Dyslipidemia was associated with the presence of cardiomyopathy, and hypertension with the occurrence of a more severe condition. Our findings could be explained by a multifactorial model of chronic CD pathogenesis, in which clinical outcomes are shaped by the combined effects of parasite diversity, multiclonality, host factors, and historical epidemiological exposures. These results highlight the need for integrative approaches to better understand disease progression.