Use of Kidneys From Trypanosoma Cruzi–Infected Donors in Naive Transplant Recipients Without Prophylactic Therapy

Abstract

Chagas disease is a lifelong parasitic infection caused by the flagellate protozoan Trypanosoma cruzi and transmitted by reduviid bugs of the Triatominae subfamily, from mother to child, by blood transfusion, by transplantation, and by ingestion of food or liquid contaminated with T. cruzi (1). In transplantation, the risk of infection depends on the donor parasite load and the specific organ involved (2). With the exception of heart transplantation, infected donors can provide acceptable organs with appropriate informed consent (3, 4). The scarcity of organs and the growing number of T. cruzi–infected donors highlight the lack of information regarding transplantation of T. cruzi–infected organs. We herein report kidney transplantation from infected donors to six seronegative recipients without prophylaxis at a center in an endemic area. CASES Donors and recipients were assessed for T. cruzi by serological tests, indirect hemagglutination, enzyme-linked immunosorbent assay, and/or indirect immunofluorescence assay. At our center, if T. cruzi–seropositive living donors present with cardiomyopathy and/or digestive megasyndrome caused by Chagas disease, donation is not accepted. Recipients signed an informed consent form, acknowledging the risk involved. From 2007 to 2013, 73 renal transplants were performed at our center, and six (8%) patients with no history of Chagas disease received kidneys from T. cruzi–infected donors. The recipients did not receive prophylactic treatment for Chagas disease. They were screened using the thick-blood-film technique once per week for the first 3 months after transplantation and once per month thereafter. In case of infection, treatment would comprise benznidazole (5 mg/kg/d for 60–90 days). The immunosuppressive regimen included tacrolimus, sodium mycophenolate, and corticosteroids at conventional doses. Four patients received induction therapy with thymoglobulin or basiliximab. Table 1 describes the patients’ characteristics, creatinine levels, and outcomes. The median time on dialysis was 3 years (range, 1–5 years). The median follow-up time was 36 months (range, 7–60 months). Living donor infected with T. cruzi received benznidazole at 5 mg/kg/d for 1 month before donation, without adverse events. None of the recipients showed any symptoms or signs of Chagas disease. One patient lost his graft secondary to rejection 3 years after transplantation. Another patient died of septic shock related to a urinary tract infection 7 months after transplantation, with a functioning graft and no signs of T. cruzi infection. DISCUSSION Although naive recipients have been treated prophylactically in reported cases, frequent monitoring is recommended over prophylactic treatment based on transmission rates, the significant side effects of benznidazole or nifurtimox, and the fact that prophylaxis may mask or mimic symptoms of transmission, such as fever and headaches (3, 5). Chagas disease in the acute phase is diagnosed by direct techniques because of delayed or absent serological conversion in immunosuppressed patients (3). Polymerase chain reaction techniques can identify positive results before parasitemia is detectable by microscopy (6). Acute T. cruzi infection is asymptomatic or presents with mild fever or other nonspecific symptoms (1, 4). During this stage, organ and tissue damage is caused by the parasite and the acute immuno-inflammatory response to the parasite (1, 7). In the chronic phase, after 8 to 12 weeks, serologic tests are necessary for diagnosis (2, 3, 8). The course of Chagas disease depends on the interaction of immune-mediated parasite control and damaging inflammation of the host tissues (1). Approximately 20% to 30% of infected patients develop cardiac and/or gastrointestinal disease with significant morbidity and mortality (1, 4). In a study performed in Argentina, 18.7% of patients who received T. cruzi–seropositive organs were infected; all patients recovered from acute infection, and one patient had relapse 3 years after transplantation (5). In a report from the United States, the infection rate among kidney recipients was 13%—those patients who were more closely monitored were diagnosed sooner and treated earlier in the course of infection (9); and in a Brazilian case series, nine renal recipients transplanted with T. cruzi–infected organs received benznidazole (5 mg/kg/d) for 14 days starting on day 0, and none of them developed the disease (10). Our promising results suggest that the use of kidneys from T. cruzi–infected donors can be considered for recipients who are properly informed and who provide consent. Of note, one recipient died at 7 months, so there may not have been enough time to exclude transmission in that case. This algorithm seems appropriate for kidney transplant recipients; however, further research is needed in other organ transplant populations with higher rates of transmission. The risk-benefit profile of prophylactic therapy should be considered. Furthermore, frequent monitoring of T. cruzi infection in recipients is essential to detect the parasite early and commence treatment promptly to eliminate the infection. Federico Cicora, MD 1,2 Verónica Escurra, MD1 Sergio Silguero, MD1 Ignacio M. González, MD1 Javier E. Roberti2 1 Renal Transplantation Hospital Alta Complejidad Pte JD Peroń Formosa, Argentina 2 Foundation for Research and Assistance in Renal Disease (FINAER) Buenos Aires, Argentina