Chagas’ Disease
F. Y. Liew in Vaccination Strategies of Tropical Diseases, 2017
Not much more is known about GP72, other than the fact that a monoclonal antibody specific for a GP72 epitope has been shown to inhibit the differentiation of T. cruzi from epimastigotes into trypomastigotes inside permeable chambers implanted s.c. into mice.109 One obvious implication of this finding is that GP72 plays a key role in the epimastigote- trypomastigote transition. However, since the noted phenomenon occurred within a mammalian host, where epimastigote-trypomastigote transformation supposedly does not normally take place, the significance of this interesting observation remains enigmatic.
Trypanosoma cruzi
Dongyou Liu in Handbook of Foodborne Diseases, 2018
This technique consists of cultivating blood samples from the patient. There are several culture media that allow the isolation of T. cruzi, some are of the cell type and therefore allow replication of the cycle of the parasite, mainly trypomastigote/amastigote; another is the biphasic medium containing a solid phase as blood agar and a liquid as fetal bovine serum; and finally monophasic means the main exponent is the liver infusion broth medium in which the epimastigote forms grow freely. The cultures are analyzed under the microscope at 20, 30, and 45 days looking for forms of epimastigotes. [66].
The Renewal of Interest in Nitroaromatic Drugs
Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay in Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Compound (30) (Figure 9) presented threefold higher in vitro activity than nifurtimox (8) against epimastigote forms of Y strain of T. cruzi. In the cytotoxicity assay, metronidazole (6) (Figure 1) presented an IC50 value of 28.05 μM (Selectivity index (SI) = cytotoxicity/activity ratio = 26.71) against J774 cells (Palace-Berl et al. 2013).
Phenotypic screening approaches for Chagas disease drug discovery
Published in Expert Opinion on Drug Discovery, 2018
Eric Chatelain, Jean-Robert Ioset
Although whether an anti-T. cruzi compound should target all parasite stages is still open to debate, there is consensus within the scientific community on disregarding the vector epimastigote form of the parasite and prioritizing the intracellular amastigotes that persist in the chronic phase of the infection. The fact that azoles are not active against the non-replicative form of T. cruzi, i.e. the trypomastigote (which is not surprising given their mechanism of action) and failed in clinical trials, pointed to the possibility of having compounds targeting both the intracellular replicative amastigote and the non-replicative trypomastigote, highlighting the need for a trypomastigote assay. Unfortunately, neither tissue culture trypomastigote (TCT) nor blood trypomastigotes (BT) isolated from infected mice are particularly amenable to high-throughput assays. Moreover, recent data with a specific class of compound suggest that in vitro activity against the trypomastigote form of T. cruzi (in a given assay) is not essential for curative efficacy in vivo (personal communication).
Plant-made vaccines against parasites: bioinspired perspectives to fight against Chagas disease
Published in Expert Review of Vaccines, 2021
Abel Ramos-Vega, Elizabeth Monreal-Escalante, Eric Dumonteil, Bernardo Bañuelos-Hernández, Carlos Angulo
Trypanosoma cruzi goes through different biological stages in its life cycle (Figure 1). The triatomine vector initially hosts the epimastigote, which multiplies by binary fission in the digestive tract [28]. Once the hindgut has been reached, the parasite differentiates into metacyclic trypomastigotes that can be expelled with the feces while blood-feeding and/or infecting host cells neighboring the bite [29,30]. Once inside cells, T. cruzi differentiates into the intracellular amastigote replicative form [31]. When replication is achieved, T. cruzi returns to the trypomastigote stage that finally lyses the infected cell, leading parasites to spread through the bloodstream to other cells and tissues. The cycle is completed when the bug sucks blood from a host infected with T. cruzi trypomastigotes [32]. In each parasite form, several proteins are expressed to play relevant roles during infection and pathogenesis (Figure 1). They include Tc24 and Tc52, which are expressed in all parasite stages; TSA-1 and TS play an important role in trypomastigotes; ASP-2 is expressed in amastigotes or cruzipain and involved in immune modulation and evasion in the mammalian host.
Oxidative stress implications for therapeutic vaccine development against Chagas disease
Published in Expert Review of Vaccines, 2021
Subhadip Choudhuri, Lizette Rios, Juan Carlos Vázquez-Chagoyán, Nisha Jain Garg
Studies examining infection dynamics and parasite tropism failed to identify the organs, tissues, or cells that play a crucial role in the recrudescence of T. cruzi during chronic stage and may play an important role in clinical manifestations of CD. Yet, some studies showed that T. cruzi trypomastigotes can transition from an amastigote-like stage to an epimastigote-like morphological form that have the capability to initiate the recurrence of infection by invading the phagocytes and cardiac cells [26]. Others identified non-proliferative dormant amastigotes, which were resistant to anti-parasitic drugs and able to reestablish infection by converting to trypomastigotes even after 30 days of drug exposure [27]. These findings suggest that the dormancy state of T. cruzi accounts for the failure of potential therapeutic drugs and complete cure of infection.
Related Knowledge Centers
- African Trypanosomiasis
- Chagas Disease
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- Parasitism
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- Trypanosoma Cruzi
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- Intracellular Parasite
- Triatominae