Chagas Disease: Still Many Unsolved Issues

Alvarez, José Mosig; Fonseca, Raíssa; Silva, Henrique Borges da; Marinho, Cláudio Romero Farias; Bortoluci, Karina Ramalho; Sardinha, Luiz Roberto; Epiphânio, Sabrina; Lima, Maria Regina D'Império

doi:10.1155/2014/912965

Cited by 33 publications

(43 citation statements)

References 66 publications

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“…About 10,000 people die from the disease each year worldwide (WHO, 2015). The migration of infected individuals to non-endemic countries turned Chagas' disease into an emerging worldwide public health problem (Coura and Viñas, 2010; Álvarez et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Infectivity and Evasion Derived from Microvesicles Cargo Produced by Trypanosoma cruzi

Borges

Uehara

Dias

et al. 2016

Front. Cell. Infect. Microbiol.

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Cell invasion by the intracellular protozoans requires interaction of proteins from both the host and the parasite. Many parasites establish chronic infections, showing they have the potential to escape the immune system; for example, Trypanosoma cruzi is an intracellular parasite that causes Chagas disease. Parasite internalization into host cell requires secreted and surface molecules, such as microvesicles. The release of microvesicles and other vesicles, such as exosomes, by different eukaryotic organisms was first observed in the late twentieth century. The characterization and function of these vesicles have recently been the focus of several investigations. In this review, we discuss the release of microvesicles by T. cruzi. The molecular content of these vesicles is composed of several molecules that take place during parasite-host cell interaction and contribute to the parasite-driven mechanism of evasion from the host immune system. These new findings appear to have a profound impact on the comprehension of T. cruzi biology and highlight novel potential strategies for developing more efficient therapeutic approaches.

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Section: Introductionmentioning

confidence: 99%

Mechanisms of Infectivity and Evasion Derived from Microvesicles Cargo Produced by Trypanosoma cruzi

Borges

Uehara

Dias

et al. 2016

Front. Cell. Infect. Microbiol.

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“…More problematic is the symptomatic chronic phase of Chagas disease, characterized by low levels of parasitemia but increased tissue injury, resulting in severe digestive and/or cardiac damage that can be lethal if the patient is untreated (3).…”

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confidence: 99%

Nitrotriazole-Based Compounds as Antichagasic Agents in a Long-Treatment In Vivo Assay

Papadopoulou

Bloomer

Rosenzweig

et al. 2017

Antimicrob Agents Chemother

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3-Nitrotriazole-based compounds belonging to various chemical subclasses were found to be very effective against Chagas disease both in vitro and in vivo after a short administration schedule. In this study, five compounds with specific characteristics were selected to be administered for longer periods of time to mice infected with the virulent Trypanosoma cruzi Y strain to further evaluate their effectiveness as antichagasic agents and whether or not potential adverse effects occur. Benznidazole was included for comparison purposes. Complete parasitemia depletion, weight gain, 100% survival, and a lack of myocardial inflammation were observed with four of the compounds and benznidazole administered intraperitoneally at 15 or 20 mg/kg of body weight/day for 40 days. There was a significant reduction in the number of treatment days (number of doses) necessary to induce parasitemia suppression with all four compounds compared to that required with benznidazole. Partial cures were obtained with only one compound tested at 15 mg/kg/day and on the schedule mentioned above but not with benznidazole. Taken together, our data suggest that these compounds demonstrate potent trypanocidal activity comparable to or better than that of the reference drug, benznidazole, when they are administered at the same dose and on the same schedule.

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“…Par ailleurs, la révision des hypothèses concernant le ou les mécanismes physiopathologiques à l'oeuvre dans les formes chroniques, et notamment dans celles se traduisant par une myocardite (90 %) [7], a conduit certains auteurs, puis l'OMS, à recommander, à rebours du paradigme qui était en cours jusqu'en 2006, un traitement étiologique systématique de la phase dite indéterminée ou de celle des complications avérées de la maladie, quelle que soit son ancienneté [21]. Les résultats de la première étude multicentrique randomisée d'envergure, en double insu contre placebo, destinée à éva-luer sur le long terme (5 à 7 ans) l'intérêt de ce traitement sont hélas bien en deçà de ce qui était espéré [15].…”

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Le troisième et nouveau visage de la maladie de Chagas

Pays

2016

Bull. Soc. Pathol. Exot.

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After the publication of the results of the BENEFIT study concluding that the benznidazole (5 mg/kg/d/60 d) is ineffective to stop the progression of the established Chagas' cardiomyopathy in adults, the author evokes the new experiences and the new challenges of 2016 regarding Chagas disease while speculating on its future and by calling back some elements little known of his history, in particular the fact that it is Chagas who invented about it to some extent the concept of "neglected disease".

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Chagas Disease: Still Many Unsolved Issues

Cited by 33 publications

References 66 publications

Mechanisms of Infectivity and Evasion Derived from Microvesicles Cargo Produced by Trypanosoma cruzi

Mechanisms of Infectivity and Evasion Derived from Microvesicles Cargo Produced by Trypanosoma cruzi

Nitrotriazole-Based Compounds as Antichagasic Agents in a Long-Treatment In Vivo Assay

Le troisième et nouveau visage de la maladie de Chagas

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