Preclinical and clinical evidence of exercise training as a complementary Chagas disease treatment

Abstract

Background: Chagas disease (ChD) is a neglected condition closely correlated to poverty and the leading cause of infectious cardiomyopathy worldwide. Although contraindicated in the past, exercise training (ET) was recently suggested as a complementary treatment for ChD. However, the mechanistic basis that supports this recommendation is still unclear. Aim: We used a systematic review framework to investigate the preclinical and clinical evidence on the relevance of ET for ChD management. Methods: A two-level PRISMA- based search was applied to PubMed/Medline, Web of Science, Scopus, and Embase databases. Parasitological, biochemical, immunological and cardiorespiratory outcomes were investigated. Results: Preclinical evidence indicates that preinfection exercise training is safe and increases host resistance to T. cruzi infection by upregulating heart and cardiomyocytes contractile function, immune (e.g., INF-γ, TNF-α, NO) and antioxidants (e.g. CAT, GR, GPx, SOD) defenses; attenuating parasitemia, parasite load, reactive oxygen (ROS) and nitrogen (RNS) species biosynthesis, cardiac and skeletal muscle molecular and microstructural damage. Conversely, concomitant infection-exercise training can exacerbate cell parasitism, proinflammatory and prooxidant responses (e.g., lipid and protein oxidation); potentiating target organs damage. Additionally, clinical evidence indicates that dosimetry-adjusted (e.g., symptom-limited exercise tests) aerobic training is equally safe to improve exercise tolerance, cardiorespiratory function and quality of life in patients with chronic ChD. Conclusion: Preclinical and clinical evidence support ET as a complementary strategy for ChD treatment, indicating that training dosimetry and infection stage must be strictly controlled to ensure cardiovascular, immunological and parasitological benefits free from adverse events.