Biological markers for evaluating therapeutic efficacy in Chagas disease, a systematic review

Pinazo, María Jesús; Thomas, M. Carmen; Búa, Jacqueline; Perrone, Alina E.; Schijman, Alejandro G.; Viotti, Rodolfo-Jorge; Ramsey, Janine-M; Ribeiro, Isabela; Sosa-Estáni, Sergio; López, Manuel Carlos; Gascón, Joaquim

doi:10.1586/14787210.2014.899150

Cited by 93 publications

(101 citation statements)

References 84 publications

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“…Among the 15mer variants, maximal performance was recorded for TSSA-CL [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] (90.18%), followed by TSSA-CL [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] (56.86%) and TSSA-CL 42-56 (40.81%) (Fig. 1C).…”

Section: Resultsmentioning

confidence: 99%

“…The TSSA-CL [42][43][44][45][46][47][48][49][50] and TSSA-CL 36-44 deletion variants displayed modest prevalences (37.26% and 33.33%, respectively), whereas TSSA-CL [30][31][32][33][34][35][36][37][38] and TSSA-CL 48-56 yielded negative results for every serum sample tested. Based on these findings, we conclude that the serodiagnostic performance of the 15mer TSSA-CL [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] relies on residues present in both 9mer variants that in concert cover TSSA-CL [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] (TSSA-CL [30][31]…”

Section: Resultsmentioning

confidence: 99%

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Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Balouz

Camara

Canepa

et al. 2015

Clin. Vaccine Immunol.

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The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide-and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acidlong peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease. Chagas disease is a major health and economic problem in Latin America, for which no vaccine or appropriate drugs for largescale public health interventions are yet available (1). It is caused by the protozoan Trypanosoma cruzi, found throughout the American continents in a variety of wild and domestic mammalian reservoirs, and it is transmitted by the bite of infected bloodsucking triatomine bugs. It is estimated that 8 to 10 million people are currently infected with T. cruzi and that up to 120 million individuals living in areas that are endemic for the parasite are at risk of infection (1). Increasing travel and immigration have also brought the risk of T. cruzi infection into countries that are not endemic for the parasite (2). Several efforts have successfully been undertaken to control transmission in Latin America, with a concomitant decrease in the actual numbers of acute vector-borne infections (3). However, humans can also become infected with T. cruzi through the ingestion of tainted food and fluids, receipt of contaminated blood transfusion or organ transplantation, and from mother-to-child during pregnancy/delivery (4).The diagnosis of Chagas disease is challenging because it is often asymptomatic in its acute phase and evolves into a chronic stage in which the disease course takes different clinical forms (1). In addition, and due to a major decline in parasitemia during the chronic phase, the detection of T. cruzi in blood sample...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Balouz

Camara

Canepa

et al. 2015

Clin. Vaccine Immunol.

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“…The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The treatment of chronic patients consists of control of the symptoms and improvement in quality of life, by preventing cardiovascular complications according to the guidelines for treating heart failure and arrhythmias [14] . Regardless of the mechanisms underlying the initiation and maintenance of the myocarditis, the bulk of the evidence indicates that the inflammatory infiltrate is a significant effector of heart tissue damage.…”

Section: Topic Highlightmentioning

confidence: 99%

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

Ferreira¹,

Frade²,

Baron³

et al. 2014

WJC

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Chagas disease cardiomyopathy (CCC), the main consequence of Trypanosoma cruzi (T.cruzi ) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon (IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease.

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“…Also, the majority of currently used methods employ crude antigen preparations from parasite life-cycle stages not present in the mammalian host. Polymerase chain reaction is the standard method of cure in the current clinical trials and although useful, there is no proof of efficacy and it is only an indication of sterile cure for a given therapy 69 . Newer tests using recombinant proteins or peptides may be an improvement, but results are often inconsistent 70 .…”

Section: Biomarkersmentioning

confidence: 99%

Current and Future Chemotherapy for Chagas Disease

Gaspar¹,

Moraes²,

Freitas‐Junior³

et al. 2015

CMC

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American trypanosomiasis, commonly called Chagas disease, is one of the most neglected illnesses in the world and remains one of the most prevalent chronic infectious diseases of Latin America with thousands of new cases every year. The only treatments available have been introduced five decades ago. They have serious, undesirable side effects and disputed benefits in the chronic stage of the disease -a characteristic and debilitating cardiomyopathy and/or megavisceras. Several laboratories have therefore focused their efforts in finding better drugs. Although recent years have brought new clinical trials, these are few and lack diversity in terms of drug mechanism of action, thus resulting in a weak drug discovery pipeline. This fragility has been recently exposed by the failure of two candidates, posaconazole and E1224, to sterilely cure patients in phase 2 clinical trials. Such setbacks highlight the need for continuous, novel and high quality drug discovery and development efforts to discover better and safer treatments.In this article we will review past and current findings on drug discovery for Trypanosoma cruzi made by academic research groups, industry and other research organizations over the last half century. 2We will also analyze the current research landscape that is now better placed than ever to deliver alternative treatments for Chagas disease in the near future.

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Biological markers for evaluating therapeutic efficacy in Chagas disease, a systematic review

Cited by 93 publications

References 84 publications

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

Current and Future Chemotherapy for Chagas Disease

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