title: Molecular identification of Trypanosoma cruzi discrete typing units in end-stage chronic Chagas heart disease and reactivation after heart transplantation.
abstract: 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 degrees S-27 degrees 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.
authors.affiliation: Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Ingeniería Genética y Biología Molecular, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Burgos
authors.forename: Mirta
authors.initials: M
authors.lastname: Diez
authors.forename: Carlos
authors.initials: C
authors.lastname: Vigliano
authors.forename: Margarita
authors.initials: M
authors.lastname: Bisio
authors.forename: Marikena
authors.initials: M
authors.lastname: Risso
authors.forename: Tomás
authors.initials: T
authors.lastname: Duffy
authors.forename: Carolina
authors.initials: C
authors.lastname: Cura
authors.forename: Betina
authors.initials: B
authors.lastname: Brusses
authors.forename: Liliana
authors.initials: L
authors.lastname: Favaloro
authors.forename: María Susana
authors.initials: MS
authors.lastname: Leguizamon
authors.forename: Raul Horacio
authors.initials: RH
authors.lastname: Lucero
authors.forename: Ruben
authors.initials: R
authors.lastname: Laguens
authors.forename: Mariano Jorge
authors.initials: MJ
authors.lastname: Levin
authors.forename: Roberto
authors.initials: R
authors.lastname: Favaloro
authors.forename: Alejandro Gabriel
authors.initials: AG
authors.lastname: Schijman
mesh_terms: D000293:Adolescent; D000328:Adult; D002598:Chagas Cardiomyopathy / Q000175:diagnosis* / Q000469:parasitology* / Q000628:therapy; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006321:Heart / Q000469:parasitology; D016027:Heart Transplantation; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D012008:Recurrence; D014349:Trypanosoma cruzi / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents