Journal Article

Molecular Identification of <i>Trypanosoma cruzi</i> Discrete Typing Units in End-Stage Chronic Chagas Heart Disease and Reactivation after Heart Transplantation

Juan Miguel Burgos, Mirta Diez, Carlos Vigliano, Margarita Bisio, Marikena Risso, Tomás Duffy, Carolina Cura, Betina Brusses, Liliana Favaloro, María Susana Leguizamon, Raul Horacio Lucero, Ruben Laguens, Mariano Jorge Levin, Roberto Favaloro and Alejandro Gabriel Schijman

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 5, pages 485-495
Published in print September 2010 | ISSN: 1058-4838
Published online September 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/655680
Molecular Identification of Trypanosoma cruzi Discrete Typing Units in End-Stage Chronic Chagas Heart Disease and Reactivation after Heart Transplantation

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Background. One hundred years after the discovery of Chagas disease, it remains a major neglected tropical disease. Chronic Chagas heart disease (cChHD) is the most severe manifestation. Heart transplantation is the proper treatment for end-stage heart failure, although reactivation of disease may result after receipt of immunosuppressive therapy. T. cruzi strains cluster into 6 discrete typing units (DTUs; I-VI) associated with different geographical distribution, transmission cycles and varying disease symptoms. In the southern cone of South America, T. cruzi II, V, and VI populations appear to be associated with Chagas disease and T. cruzi I with sylvatic cycles.

Methods. Molecular characterization of DTUs, T. cruzi I genotypes (on the basis of spliced-leader gene polymorphisms), and minicircle signatures was conducted using cardiac explant specimens and blood samples obtained from a cohort of 16 Argentinean patients with cChHD who underwent heart transplantation and from lesion samples obtained from 6 of these patients who presented with clinical reactivation of Chagas disease.

Results. Parasite persistence was associated with myocarditis progression, revealing T. cruzi I (genotype Id) in 3 explant samples and T. cruzi II, V, or VI in 5 explant samples. Post-heart transplantation follow-up examination of bloodstream DTUs identified T. cruzi I in 5 patients (genotypes Ia or Id) and T. cruzi II, V, or VI in 7 patients. T. cruzi I, V, and VI were detected in skin chagoma specimens, and T. cruzi V and VI were detected in samples obtained from patients with myocarditis reactivations. Multiple DTUs or genotypes at diverse body sites and polymorphic minicircle signatures at different cardiac regions revealed parasite histotropism. T. cruzi I infections clustered in northern Argentina (latitude, 23°S–27°S), whereas T. cruzi II, V, or VI DTUs were more ubiquitous.

Conclusions. Multiple DTUs coexist in patients with Chagas disease. The frequent finding of T. cruzi I associated with cardiac damage was astounding, revealing its pathogenic role in cChHD at the southern cone.

Journal Article.  5091 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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