Chagas Disease Pathogenesis and Therapeutic Approaches

Chagas disease arises from infection by the protozoan parasite Trypanosoma cruzi and manifests in acute and chronic phases. During the acute stage, parasites circulate and invade a range of tissues, differentiating into intracellular amastigotes that replicate within host cells. As the infection progresses, a proportion of individuals develop chronic cardiomyopathy or gastrointestinal complications decades after initial exposure. Pathogenesis reflects a complex interplay between persistent low‐level parasitaemia, discrete tissue reservoirs and host immune responses, with inflammatory damage, microvascular disturbances and fibrosis driving organ dysfunction. Current antiparasitic drugs, notably benznidazole and nifurtimox, achieve parasitological clearance in early infection but afford limited benefit in established chronic disease and incur significant toxicity. Recent advances seek to refine combination regimens that target both parasite and host metabolic pathways, to deploy immunomodulatory or vaccine strategies and to exploit novel small molecules inhibiting key parasite enzymes. Integrating molecular insights into tissue‐specific host–parasite interactions with innovative therapeutic modalities holds promise for more effective intervention and improved clinical outcomes.

Research from Nature Portfolio

Recent studies have revealed region‐specific alterations in cardiac small molecules during chronic infection, correlating with predilection sites for apical aneurysm formation. Standard benznidazole therapy incompletely restores the myocardial biochemical milieu, whereas a reduced‐dose benznidazole regimen combined with an adjuvant immunotherapy achieves superior normalisation of cardiac small molecule profiles despite only modest additional parasite clearance. This work elucidates the molecular basis for treatment failure and highlights the value of strategies that act simultaneously on parasite burden and host metabolic recovery to mitigate chronic cardiac sequelae.

Chagas Disease Pathogenesis and Therapeutic Approaches publication trend

The graph below shows the total number of articles in chagas disease pathogenesis and therapeutic approaches across all publications each year (not limited to Nature Index journals).

Technical terms

Trypanosoma cruzi: A kinetoplastid protozoan parasite and causative agent of Chagas disease.

Amastigote: The intracellular, non‐flagellated replicative form of T. cruzi within host cells.

Trypomastigote: The extracellular, flagellated infective stage of T. cruzi circulating in the bloodstream.

Benznidazole: A nitroimidazole‐derived antiparasitic drug used as first‐line therapy for Chagas disease.

Immunotherapy: A treatment modality that harnesses or modulates the host immune system to enhance pathogen clearance.

Cytochrome bc₁ complex: A mitochondrial enzyme complex in T. cruzi involved in electron transport, targeted by specific inhibitors.

References

1. Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease. Nature Communications (2023).
2. Short-course combination treatment for experimental chronic Chagas disease. Science Translational Medicine (2023).
3. Immunoglobulin and T cell receptor repertoire changes induced by a prototype vaccine against Chagas disease in naïve rhesus macaques. Journal of Biomedical Science (2024).