Abstract
The most severe clinical symptomatology of Chagas disease affects ~30% of those chronically infected with the Trypanosoma cruzi parasite. The pathogenic mechanisms that lead to life-threatening heart and gut tissue disruptions occur “silently” for a longtime in a majority of cases. As a result, despite there are several serological and molecular methods available to diagnose the infection in its acute and chronic stages, diagnosis is often achieved only after the onset of clinical symptoms in the chronic phase of the disease. Furthermore, although there are two drugs to treat it, the assessment of their performance is impractical with current parasite-derived diagnostics, and therapeutic efficacy cannot be acknowledged in a timely manner.
In this chapter we present two procedures to measure host-derived molecules as surrogates of therapeutic response against chronic T. cruzi infection. Their outputs relate to the generation and activity of thrombin, a major component of the blood coagulation cascade. This is due to the fact that a hypercoagulability state has been described to occur in chronic Chagas disease patients and revert after treatment with benznidazole.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Maeda FY, Cortez C, Alves RM, Yoshida N (2012) Mammalian cell invasion by closely related Trypanosoma species T. dionisii and T. cruzi. Acta Trop 121(2):141–147
Grauert MR, Houdayer M, Hontebeyrie-Joskowciz M (1993) Trypanosoma cruzi infection enhances polyreactive antibody response in an acute case of human Chagas’ disease. Clin Exp Immunol 93(1):85–92
Cardillo F, Voltarelli JC, Reed SG, Silva JS (1996) Regulation of Trypanosoma cruzi infection in mice by gamma interferon and interleukin 10: role of NK cells. Infect Immun 64(1):128–134
Gascon J, Pinazo M-J (2015) Chagas disease: from Latin America to the world. Rep Parasitol 4:7
Schijman AG (2018) Molecular diagnosis of Trypanosoma cruzi. Acta Trop 184:59–66
Abras A, Gállego M, Llovet T, Tebar S, Herrero M, Berenguer P, Ballart C, Martí C, Muñoz C (2016) Serological diagnosis of chronic Chagas disease: is it time for a change? J Clin Microbiol 54(6):1566–1572
Zrein M, Granjon E, Gueyffier L et al (2018) A novel antibody surrogate biomarker to monitor parasite persistence in Trypanosoma cruzi-infected patients. PLoS Negl Trop Dis 12(2):e0006226
Pinazo M-J, Thomas MC, Bua J et al (2014) Biological markers for evaluating therapeutic efficacy in Chagas disease, a systematic review. Expert Rev Anti-Infect Ther 12(4):479–496
Egüez KE, Alonso-Padilla J, Terán C, Chipana Z, García W, Torrico F, Gascon J, Lozano-Beltran D-F, Pinazo M-J (2017) Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis. PLoS Negl Trop Dis 11(4):e0005501
Keating SM, Deng X, Fernandes F et al (2015) Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease. Int J Cardiol 199:451–459
Pinazo M-J, Tàssies D, Muñoz J, Fisa R, Posada EDJ, Monteagudo J, Ayala E, Gállego M, Reverter J-C, Gascon J (2011) Hypercoagulability biomarkers in Trypanosoma cruzi-infected patients. Thromb Haemost 106(4):617–623
Ndao M, Spithill TW, Caffrey R et al (2010) Identification of novel diagnostic serum biomarkers for Chagas’ disease in asymptomatic subjects by mass spectrometric profiling. J Clin Microbiol 48(4):1139–1149
Curvo EO, Ferreira RR, Madeira FS, Alves GF, Chambela MC, Mendes VG, Sangenis LHC, Waghabi MC, Saraiva RM (2018) Correlation of transforming growth factor-beta1 and tumour necrosis factor levels with left ventricular function in Chagas disease. Mem Inst Oswaldo Cruz 113(4):e170440
Okamoto EE, Sherbuk JE, Clark EH et al (2014) Biomarkers in Trypanosoma cruzi-infected and uninfected individuals with varying severity of cardiomyopathy in Santa Cruz, Bolivia. PLoS Negl Trop Dis 8(10):e3227
Herrera R, Diaz E, Perez Aguilar R, Bianchi J, Berman S, Luciardi HL (2005) Prothrombotic state in early stages of chronic Chagas’ disease. Its association with thrombotic risk factors. Arch Cardiol Mex 75(Suppl 3):38–48
Pinazo M-J, Posada Ede J, Izquierdo L et al (2016) Altered hypercoagulability factors in patients with chronic Chagas disease: potential biomarkers of therapeutic response. PLoS Negl Trop Dis 10(1):e0004269
Engelmann B, Massberg S (2013) Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 13(1):34–45
Schuetz P, Christ-Crain M, Morgenthaler NG, Struck J, Bergmann A, Müller B (2007) Circulating precursor levels of endothelin-1 and adrenomedullin, two endothelium-derived, counteracting substances, in sepsis. Endothelium 14(6):345–351
Kreutz RP, Tantry US, Bliden KP, Gurbel PA (2007) Inflammatory changes during the “common cold” are associated with platelet activation and increased reactivity of platelets to agonists. Blood Coagul Fibrinolysis 18(8):713–718
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Alonso-Padilla, J., Tassies, D., Cortes-Serra, N., Gascon, J., Reverter, JC., Pinazo, MJ. (2019). Host-Derived Molecules as Novel Chagas Disease Biomarkers: Hypercoagulability Markers in Plasma. In: Gómez, K., Buscaglia, C. (eds) T. cruzi Infection. Methods in Molecular Biology, vol 1955. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9148-8_21
Download citation
DOI: https://doi.org/10.1007/978-1-4939-9148-8_21
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-9147-1
Online ISBN: 978-1-4939-9148-8
eBook Packages: Springer Protocols