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Intra-host Trypanosoma cruzi strain dynamics shape disease progression: the missing link in Chagas disease
Eric Dumonteil1, Hans Desale1, Weihong Tu1
1Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University , New Orleans, Louisiana, USA.
Insights
Increased Trypanosoma cruzi parasite diversity in hosts hinders parasite multiplication and Chagasic cardiomyopathy progression. This finding offers new insights into Chagas disease pathogenesis and risk stratification.
Area of Science:
- Infectious Diseases
- Parasitology
- Cardiology
Background:
- Chronic Chagasic cardiomyopathy affects 20-40% of patients years after Trypanosoma cruzi infection.
- Disease progression and risk factors for severe cardiac disease remain poorly understood.
Purpose of the Study:
- To investigate the relationship between Trypanosoma cruzi parasite dynamics, diversity, and Chagasic cardiomyopathy progression.
- To identify potential biomarkers for disease progression.
Main Methods:
- Longitudinal study of naturally Trypanosoma cruzi-infected rhesus macaques over 2.5 years.
- Monitoring of parasite (Trypanosoma cruzi) dynamics, parasitemia, and parasite strain diversity.
- Assessment of electrocardiographic (ECG) profiles and plasma fibronectin degradation.
Main Results:
- Higher parasite diversity correlated with better parasitemia control and decreased parasite multiplication rate.
- Increasing parasitemia and lower parasite diversity were associated with progressive ECG changes.
- Plasma fibronectin degradation was linked to Chagasic cardiomyopathy progression.
Conclusions:
- Trypanosoma cruzi parasite diversity plays a crucial role in shaping Chagas disease pathogenesis and cardiomyopathy progression.
- Increased parasite diversity appears protective against severe cardiac disease.
- Plasma fibronectin degradation may serve as a potential biomarker for Chagas disease progression.
Importance:
Chagas disease progression remains poorly understood, and patients at increased risk of developing severe cardiac disease cannot be distinguished from those who may remain asymptomatic. Monitoring of Trypanosoma cruzi strain dynamics and pathogenesis over 2-3 years in naturally infected macaques shows that increasing parasite diversity in hosts is detrimental to parasite multiplication and Chagasic cardiomyopathy disease progression. This provides a novel framework for the understanding of Chagas disease pathogenesis.
