An Updated View of the Trypanosoma cruzi Life Cycle: Intervention Points for an Effective Treatment

Abstract

Chagas disease (CD) is a parasitic, systemic, chronic, and often fatal illness caused by infection with the protozoan Trypanosoma cruzi . The World Health Organization classifies CD as the most prevalent of poverty-promoting neglected tropical diseases, the most important parasitic one, and the third most infectious disease in Latin America. Currently, CD is a global public health issue that affects 6–8 million people. However, the current approved treatments are limited to two nitroheterocyclic drugs developed more than 50 years ago. Many efforts have been made in recent decades to find new therapies, but our limited understanding of the infection process, pathology development, and long-term nature of this disease has made it impossible to develop new drugs, effective treatment, or vaccines. This Review aims to provide a comprehensive update on our understanding of the current life cycle, new morphological forms, and genetic diversity of T. cruzi , as well as identify intervention points in the life cycle where new drugs and treatments could achieve a parasitic cure.

Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

“…T. cruzi is typically transmitted through contaminated feces of an insect vector called triatomines or "kissing bugs," but oral transmission through ingestion of food contaminated with Triatomine feces, blood transfusions, and vertical transmission have also contributed. During the bloodmeal, male and female triatomines release feces containing flagellated parasites called trypomastigotes, which penetrate the body through the bite wound or through mucous membranes (Martıń-Escolano et al, 2022). As an obligate intracellular parasite, T. cruzi invades cells at the inoculum site (e.g.…”

Trypanosoma cruzi DNA Polymerase β Is Phosphorylated In Vivo and In Vitro by Protein Kinase C (PKC) and Casein Kinase 2 (CK2)

“…In endemic areas, the disease is transmitted by blood-sucking insects of the subfamily Triatominae, which can infect a mammalian host [ 5 ]. The T. cruzi parasite is an intracellular protozoan that can undergo a complex life cycle between the insect vector and a mammalian host [ 5 , 6 , 7 ]. The parasite adopts four main forms during its life cycle: two in the insect vector, which are epimastigotes (replicative form) and metacyclic trypomastigotes (non-replicative and infectious form) [ 5 , 6 , 7 ].…”

“…The T. cruzi parasite is an intracellular protozoan that can undergo a complex life cycle between the insect vector and a mammalian host [ 5 , 6 , 7 ]. The parasite adopts four main forms during its life cycle: two in the insect vector, which are epimastigotes (replicative form) and metacyclic trypomastigotes (non-replicative and infectious form) [ 5 , 6 , 7 ]. The mammalian host also adopts two forms, amastigote (replicative intracellular form) and blood trypomastigote (non-replicative form) [ 5 , 6 , 7 ].…”

Nitroimidazopyrazinones with Oral Activity against Tuberculosis and Chagas Disease in Mouse Models of Infection

“…10 New drugs should also achieve total clearance of parasites in patients to prevent relapse after treatment. 11 In recent years, combination therapies that utilize multiple drugs with different mechanisms of action have been found to be effective in preclinical testing. 12,13 While combinations have been tested in clinical trials, their efficacy compared to individual drug components alone have yet to be identified.…”

“…Hence, ideal TPPs focus on new regimens that have a shorter treatment course, are safe and more efficacious than current drugs, exhibit good oral bioavailability, and are active against both chronic and acute phases . New drugs should also achieve total clearance of parasites in patients to prevent relapse after treatment . In recent years, combination therapies that utilize multiple drugs with different mechanisms of action have been found to be effective in preclinical testing. , While combinations have been tested in clinical trials, their efficacy compared to individual drug components alone have yet to be identified …”