Diagnostic Applicability of Neutralizing Antibodies to Trypanosoma cruzi Trans-sialidase

  • María Susana LeguizamónEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1955)


The trans-sialidase (TS), a virulence factor expressed on the surface of Trypanosoma cruzi, the agent of Chagas disease, is an enzyme that transfers sialic acids between glycoconjugates. In humans and most tested mammals, the onset of the chronic phase of T. cruzi infection correlates with the elicitation of antibodies directed to the TS catalytic domain, which inhibit the sialyl residues transfer reaction in vitro and in vivo. The method described here, termed trans-sialidase inhibition assay (TIA), enables the detection of TS-neutralizing antibodies in serum samples of different mammalian species, without the use of conjugated secondary reagents. The high specificity and exquisite sensitivity displayed by the TIA allow to overcome the limitations of routinely used Chagas disease serodiagnostic assays.

Key words

Trans-sialidase Trans-sialidase-neutralizing antibodies TIA Trypanosoma cruzi reservoirs Trypanosoma cruzi human diagnosis 


  1. 1.
    Schmunis GA, Yadon ZE (2010) Chagas disease: a Latin American health problem becoming a world health problem. Acta Trop 115:14–212CrossRefGoogle Scholar
  2. 2.
    Requena-Mendez A, Aldasoro E, de Lazzari E et al (2015) Prevalence of Chagas disease in Latin American migrants living in Europe: a systematic review and meta-analysis. Plos Negl Trop 9:e0003540. CrossRefGoogle Scholar
  3. 3.
    Young C, Losikoff O, Chawla A et al (2007) Transfusion acquired Trypanosoma cruzi infection. Transfusion 47:540–544CrossRefGoogle Scholar
  4. 4.
    Frank M, Hegenscheid B, Janitschke K et al (1997) Prevalence and epidemiological significance of Trypanosoma cruzi infection among Latin American immigrants in Berlin, Germany. Infection 25:355–358CrossRefGoogle Scholar
  5. 5.
    Leiby DA, Herron RM, Reed EJ et al (2002) Trypanosoma cruzi in Los Angeles and Miami blood donors: impact of evolving donor demographics on seroprevalence and implications for transfusion transmission. Transfusion 42:549–555CrossRefGoogle Scholar
  6. 6.
    Luquetti A, Rassi A (2000) Diagnóstico Laboratorial da Infecçao pelo Trypanosoma cruzi. In: T. cruzi e Doença de Chagas, 2nd edn. Editora Guanabara Koogan SA, Rio de JaneiroGoogle Scholar
  7. 7.
    Caballero ZC, Sousa OE, Marques WP et al (2007) Evaluation of serological tests to identify Trypanosoma cruzi infection in humans and determine cross-reactivity with Trypanosoma rangeli and Leishmania spp. Clin Vaccine Immunol 14:1045–1049CrossRefGoogle Scholar
  8. 8.
    Frank FM, Fernández MM, Taranto NJ et al (2003) Characterization of human infection by Leishmania spp. in the Northwest of Argentina: immune response, double infection with Trypanosoma cruzi and species of Leishmania involved. Parasitology 126:31–39CrossRefGoogle Scholar
  9. 9.
    Saez-Alquezar A, Otani MM, Sabino EC et al (1998) Evaluation of the performance of Brazilian blood banks in testing for Chagas’ disease. Vox Sang 74:228–231CrossRefGoogle Scholar
  10. 10.
    World Health Organization (1991) Control Chagas disease. WHO Tech Rep Ser 811:38–47Google Scholar
  11. 11.
    Mucci J, Carmona SJ, Volcovich R et al (2017) Next generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes. PLoS Negl Trop Dis 11(10):e0005972. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Frasch AC, Cazzulo JJ, Aslund L et al (1991) Comparison of genes encoding Trypanosoma cruzi antigens. Parasitol Today 7:148–151CrossRefGoogle Scholar
  13. 13.
    da Silveira JF, Umezawa ES, Luquetti AO (2001) Chagas disease: recombinant Trypanosoma cruzi antigens for serological diagnosis. Trends Parasitol 17:286–291CrossRefGoogle Scholar
  14. 14.
    Balouz V, Agüero F, Buscaglia CA (2017) Chagas disease diagnostic applications: present knowledge and future steps. Adv Parasitol 97:1–45. CrossRefPubMedGoogle Scholar
  15. 15.
    Clough B, Atilola FA, Healy N et al (1996) Plasmodium falciparum lacks sialidase and trans-sialidase activity. Parasitology 112:443–449CrossRefGoogle Scholar
  16. 16.
    Frasch AAC (2000) Functional diversity in the trans-sialidase and mucin families in Trypanosoma cruzi. Parasitol Today 16:282–286CrossRefGoogle Scholar
  17. 17.
    Campetella O, Utaro T, Parodi AJ et al (1994) A recombinant Trypanosoma cruzi trans-sialidase lacking the amino acid repeats retains the enzymatic activity. Mol Biochem Parasitol 64:337–340CrossRefGoogle Scholar
  18. 18.
    Leguizamón MS, Campetella O, Russomando GA et al (1994) Antibodies inhibiting Trypanosoma cruzi trans-sialidase activity in sera from human infections. J Infect Dis 170:1570–1574CrossRefGoogle Scholar
  19. 19.
    Leguizamón MS, Campetella O, González Cappa SM et al (1994) Mice infected with Trypanosoma cruzi produced antibodies against the enzymatic domain of trans-sialidase that inhibit its activity. Infect Immun 62(8):3441–3446PubMedPubMedCentralGoogle Scholar
  20. 20.
    Risso MG, Pitkosvky T, Caccuri R et al (2007) Immune system pathogenesis is prevented by the neutralization of the systemic trans-sialidase from Trypanosoma cruzi during severe infections. Parasitology 134(Pt 4):503–510CrossRefGoogle Scholar
  21. 21.
    Risso MG, Garbarino GB, Mocetti E et al (2004) Differential expression of a virulence factor, the trans-sialidase, by the main Trypanosoma cruzi lineages. J Infect Dis 189(12):2250–2259CrossRefGoogle Scholar
  22. 22.
    Leguizamón MS, Russomando G, Luquetti A et al (1997) Long-lasting antibodies detected by a trans-sialidase inhibition assay of sera from parasite-free, serologically cured Chagasic patients. J Infect Dis 175:1272–1275CrossRefGoogle Scholar
  23. 23.
    Leguizamón MS, Russomando G, Almirón M et al (1998) Use of trans-sialidase inhibition assay in a Trypanosoma cruzi serologically negative group but at a high risk of infection. Clin Diagn Lab Immunol 5:254–255PubMedPubMedCentralGoogle Scholar
  24. 24.
    Blejer JL, Sartor PA, Bottasso O et al (2008) Trans-sialidase inhibition assay for the detetion of Trypanosoma cruzi infection in blood donor samples from Argentina. Vox Sang 95:189–196CrossRefGoogle Scholar
  25. 25.
    Sartor P, Cardinal MV, Orozco M et al (2011) Trans-sialidase neutralizing antibodies detection in Trypanosoma cruzi infected domestic reservoirs. Clin Vaccine Immunol 18:984–989CrossRefGoogle Scholar
  26. 26.
    Sartor P, Ceballos L, Orozco M et al (2013) Trans-sialidase inhibition assay (TIA) detects Trypanosoma cruzi infection in different wild mammal species. Vector Borne Zoonotic Dis 13:581–585CrossRefGoogle Scholar
  27. 27.
    Buchovsky S, Campetella O, Oddone R et al (2001) Trans-sialidase inhibition assay (TIA), a high sensitive and specific diagnostic technique of Chagas Disease. Clin Diagn Lab Immunol 8:187–189PubMedPubMedCentralGoogle Scholar
  28. 28.
    Sartor P, Agusti A, Leguizamón MS et al (2010) Continuous non-radioactive method for screening trypanosomal trans-sialidase activity and its inhibitors. Glycobiology 20(8):982–990CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San MartínBuenos AiresArgentina
  2. 2.Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Buenos AiresArgentina

Personalised recommendations