Early molecular diagnosis of acute Chagas disease after transplantation with organs from T. cruzi infected donors

CURA C.I.; LATTES R.; NAGEL C.; GIMENEZ M.J; BLANES M.; CALABUIG E.; IRANZO A.; BARCAN L.A.; ANDERS M.; SCHIJMAN A.G.

Barcelona

Taller; IX Taller sobre la enfermedad de Chagas: Trypanosoma cruzi, del genotipo a la Clínica; 2013

CRESIB Hospital Clínic-Universitat de Barcelona

Introduction. Chagas disease, caused by T. cruzi, is transmitted mainly by triatomine insect vectors, blood transfusion or by infected women to offspring. Amastigotes have been isolated from various organs, thus organ transplantation (Tx) appears as a novel route of transmission. The results of molecular diagnosis and of characterization of T. cruzi acute infection in naïve Tx recipients transplanted with organs from infected deceased donors (IDD) are reported. Methods. Case 1: Argentinean IDD and 3 recipients (1 lung, 1 liver, 1 kidney). Case 2: Argentinean IDD and 1 liver recipient. Case 3: IDD from Bolivia and 2 recipients (1 liver and 1 kidney-pancreas). Case 4: Argentinean IDD and 2 kidney recipients. Although other organ recipients from cases 1-4 may possibly exist, no samples were remitted for molecular diagnosis. Peripheral blood or cerebrospinal fluid (CSF) samples from recipients were collected for detection of T. cruzi by means of kinetoplastid (kDNA)-PCR. Positive samples were subjected to a PCR algorithm for identification of T. cruzi Discrete Typing Units (DTUs) and to Real-time PCR to quantify parasitic loads in blood samples. Minicircle signatures of T. cruzi infecting populations were also analyzed using RFLP-PCR. Results. Case 1: blood samples from recipients 1A (lung Tx) and 1B (liver Tx) were kDNA-PCR positive after 72 and 98 days post-Tx, respectively, and both were infected by DTU TcV. The comparison between their minicircle signatures revealed nearly identical RFLP-PCR profiles, confirming a common source of infection. Case 2: the recipient (liver Tx) exhibited positive kDNA-PCR 36 days post-Tx and was also infected by TcV. Case 3: blood samples from recipient 3A (liver Tx) were kDNA-PCR positive 43 days post-Tx and TcV was identified. Case 4: One of the recipients (kidney Tx) showed kDNA-PCR positive results 93 days after Tx and central nervous system involvement. T. cruzi infecting populations were characterized as TcV in blood. It is worth noting that there were three other kidney recipients from cases 1, 3 and 4 that did not show a positive serologic finding or kDNA-PCR result at least after 429, 580 or 298 days post-Tx, respectively. Conclusions: Molecular tools allowed for early diagnosis of acute T. cruzi infection. The routes of transmission could be inferred by fingerprinting of the detected T. cruzi populations, directly in peripheral blood and CSF samples from transplant recipients. Furthermore, this report reveals the relevance of systematic monitoring of recipients by PCR strategies in order to provide prompt diagnosis and timely anti-trypanosomal treatment.