Early polymerase chain reaction detection of Chagas disease reactivation in heart transplant patients.
BACKGROUND
Heart transplantation is a valuable therapeutic option for Chagas disease patients with severe cardiomyopathy. During patient follow-up, the differential diagnosis between cardiac transplant rejection and Chagas disease infection reactivation remains a challenging task, which hinders rapid implementation of the appropriate treatment. Herein we investigate whether polymerase chain reaction (PCR) strategies could facilitate early detection of Trypanosoma cruzi (T cruzi) in transplanted endomyocardial biopsies (EMBs).


METHODS
In this study we analyzed 500 EMB specimens obtained from 58 chagasic cardiac transplant patients, using PCR approaches targeted to nuclear (rDNA 24Sα) and kinetoplastid (kDNA) markers, and compared the efficiency of these approaches with that of other tests routinely used.


RESULTS
T cruzi DNA was detected in 112 EMB specimens derived from 39 patients (67.2%). The first positive result occurred at a median 1.0 month post-transplant. Conventional histopathologic, blood smear and hemoculture analyses showed lower sensitivity and higher median time to the first positive result. Patient follow-up revealed that 31 of 39 PCR-positive cases presented clinical reactivation of Chagas disease at different time-points after transplantation. PCR techniques showed considerable sensitivity (0.82) and specificity (0.60), with area under the receiver operating characteristic (ROC) curves of 0.708 (p = 0.001). Moreover, PCR techniques anticipated the clinical signs of Chagas disease reactivation by up to 36 months, with a median time of 6 months and an average of 9.1 months.


CONCLUSIONS
We found a good association between the PCR diagnosis and the clinical signs of the disease, indicating that the PCR approaches used herein are suitable for early diagnosis of Chagas disease reactivation, with high potential to assist physicians in treatment decisions. For this purpose, an algorithm is proposed for surveillance based on the molecular tests.
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: andrea@ufmg.br.
Priscilla Almeida
PA
da Costa
Departamento de Genética, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
Marcela
M
Segatto
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Danielle Fernandes
DF
Durso
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Wagson José
WJ
de Carvalho Moreira
Hospital das Clinicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Lucas Lodi
LL
Junqueira
Hospital das Clinicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Fábio Morato
FM
de Castilho
Hospital das Clinicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Silvio Amadeu
SA
de Andrade
Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Cláudio Léo
CL
Gelape
Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Egler
E
Chiari
Centro de Pesquisas René Rachou, Fiocruz-Minas, Grupo Integrado de Pesquisas em Biomarcadores, Belo Horizonte, Minas Gerais, Brazil.
Andréa
A
Teixeira-Carvalho
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Sergio Danilo
SD
Junho Pena
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Carlos Renato
CR
Machado
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Gloria Regina
GR
Franco
Departamento de Patologia da Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Geraldo Brasileiro
GB
Filho
Departamento de Clinica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Maria da Consolação
MDC
Vieira Moreira
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Andréa
A
Mara Macedo
D000328:Adult; D002598:Chagas Cardiomyopathy / Q000175:diagnosis* / Q000601:surgery*; D016054:DNA, Protozoan; D004699:Endocardium / Q000469:parasitology*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D014349:Trypanosoma cruzi / Q000302:isolation & purification*
D016054:DNA, Protozoan
Chagas disease reactivation; endomyocardial biopsy; heart transplantation; molecular diagnostics; polymerase chain reaction