Putting Infection Dynamics at the Heart of Chagas Disease

Abstract

In chronic Trypanosoma cruzi infections, parasite burden is controlled by effective, but non-sterilising immune responses. Infected cells are difficult to detect because they are scarce and focally distributed in multiple sites. However, advances in detection technologies have established a link between parasite persistence and the pathogenesis of Chagas heart disease. Long-term persistence likely involves episodic reinvasion as well as continuous infection, to an extent that varies between tissues. The primary reservoir sites in humans are not definitively known, but analysis of murine models has identified the gastrointestinal tract. Here, we highlight that quantitative, spatial and temporal aspects of T. cruzi infection are central to a fuller understanding of the association between persistence, pathogenesis and immunity, and for optimising treatment.

3D mapping of host-parasite-microbiome interactions reveals metabolic determinants of tissue tropism and disease tolerance in Chagas disease

“…Disease severity is tied to the balance between resistance and tolerance mechanisms 22 . Resistance reduces pathogen load, but can cause collateral damage to the host, as indeed has been observed with immune clearance of T. cruzi -infected cells 23 . In contrast, tolerance reduces disease or immune-mediated collateral damage without affecting the pathogen load 22 .…”

Evolutionary ecology of Chagas disease; what do we know and what do we need?

“…Multiclonal infections may thus be the norm rather than the exception, and the interactions among parasite genotypes within hosts are still mostly unknown, although they may lead to different infection profiles (Ragone et al., ) and have important evolutionary implications. Overall, a better understanding of the multiclonality of infection is clearly needed for a detailed understanding of parasite infection dynamics and of the evolutionary forces that modulate parasite genetic diversity (Lewis & Kelly, ).…”

“…The blood parasitemia then falls, and T. cruzi parasitizes myocytes located within cardiac, skeletal or smooth muscle tissues. Parasite persistence may then involve different mechanisms that potentially include continuous intracellular replication, dormant forms of T. cruzi and intermittent reactivation (Lewis & Kelly, ). Over the course of infection, those combine to induce local and global inflammatory responses that, together with the parasite‐mediated autoimmune response (Teixeira, Nascimento, & Sturm, ), determine the timing and intensity of Chagas disease pathology.…”

Drug-cured experimental Trypanosoma cruzi infections confer long-lasting and cross-strain protection

“…Other tissues and organs, including the heart and skeletal muscle, are infected sporadically, the extent of which is influenced by host:parasite genetics and immune status. Additional factors such as nutrition, environmental stimuli, age and co-infections could also play a role in this complex chronic infection profile [37]. The survival of the small parasite foci within apparently tolerant sites is crucial for long-term infection, although the immunological context of these reservoirs is unknown.…”