Advertisement

Host-Derived Molecules as Novel Chagas Disease Biomarkers: Hypercoagulability Markers in Plasma

  • Julio Alonso-Padilla
  • Dolors Tassies
  • Nuria Cortes-Serra
  • Joaquim Gascon
  • Joan-Carles Reverter
  • María-Jesús PinazoEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1955)

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.

Key words

Chagas disease Diagnosis Prognosis Therapeutic response Host-derived biological markers Hypercoagulability biomarkers 

References

  1. 1.
    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):141–147CrossRefGoogle Scholar
  2. 2.
    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):85–92CrossRefGoogle Scholar
  3. 3.
    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):128–134PubMedPubMedCentralGoogle Scholar
  4. 4.
    Gascon J, Pinazo M-J (2015) Chagas disease: from Latin America to the world. Rep Parasitol 4:7CrossRefGoogle Scholar
  5. 5.
    Schijman AG (2018) Molecular diagnosis of Trypanosoma cruzi. Acta Trop 184:59–66CrossRefGoogle Scholar
  6. 6.
    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):1566–1572CrossRefGoogle Scholar
  7. 7.
    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):e0006226CrossRefGoogle Scholar
  8. 8.
    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):479–496CrossRefGoogle Scholar
  9. 9.
    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):e0005501CrossRefGoogle Scholar
  10. 10.
    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 199:451–459CrossRefGoogle Scholar
  11. 11.
    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):617–623PubMedGoogle Scholar
  12. 12.
    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):1139–1149CrossRefGoogle Scholar
  13. 13.
    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):e170440CrossRefGoogle Scholar
  14. 14.
    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):e3227CrossRefGoogle Scholar
  15. 15.
    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):38–48Google Scholar
  16. 16.
    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):e0004269CrossRefGoogle Scholar
  17. 17.
    Engelmann B, Massberg S (2013) Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 13(1):34–45CrossRefGoogle Scholar
  18. 18.
    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):345–351CrossRefGoogle Scholar
  19. 19.
    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):713–718CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Julio Alonso-Padilla
    • 1
  • Dolors Tassies
    • 2
  • Nuria Cortes-Serra
    • 1
  • Joaquim Gascon
    • 1
  • Joan-Carles Reverter
    • 2
  • María-Jesús Pinazo
    • 1
    Email author
  1. 1.Barcelona Institute for Global Health (ISGlobal), Hospital Clínic – Universitat de BarcelonaBarcelonaSpain
  2. 2.Hemotherapy and Hemostasis DepartmentHospital ClínicBarcelonaSpain

Personalised recommendations