Molecular identification of Trypanosoma cruzi discrete typing units in end-stage chronic Chagas heart disease and reactivation after heart transplantation.
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.
Burgos
Juan Miguel
JM
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.
Diez
Mirta
M
Vigliano
Carlos
C
Bisio
Margarita
M
Risso
Marikena
M
Duffy
Tomás
T
Cura
Carolina
C
Brusses
Betina
B
Favaloro
Liliana
L
Leguizamon
María Susana
MS
Lucero
Raul Horacio
RH
Laguens
Ruben
R
Levin
Mariano Jorge
MJ
Favaloro
Roberto
R
Schijman
Alejandro Gabriel
AG
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
D007166:Immunosuppressive Agents