Acute chagasic myocardiopathy after orthotopic liver transplantation with donor and recipient serologically negative for Trypanosoma cruzi: A case report

Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease following solid-organ transplantation has occurred in Latin America. This report presents the occurrence of Chagas disease despite negative serological tests in both the donor and the recipient, as well as the effectiveness of treatment. A 21-year-old woman from the state of Sao Paulo (Brazil) underwent cadaveric donor liver transplantation in November 2005, due to cirrhosis of autoimmune etiology. Ten months after liver transplantation, she developed signs and symptoms of congestive heart failure (New York Heart Association functional class IV). The echocardiogram, which was normal preoperatively, showed dilated cardiac chambers, depressed left ventricular systolic function (ejection fraction = 35%) and moderate pulmonary hypertension. Clinical investigation discarded ischemic heart disease and autoimmune and other causes for heart failure. Immuno fluorescence (immunoglobulin M and immunoglobulin G) and hemagglutination tests for T cruzi were positive, and abundant T cruzi amastigotes were readily identified in myocardial biopsy specimens. Treatment with benznidazole for 2 months yielded an excellent clinical response. At the moment of submission, the patient remains in functional class I. This case highlighted that more appropriate screening for T cruzi infection is mandatory in potential donors and recipients of solid-organ transplants in regions where Chagas disease is prevalent. Moreover, it stressed that this diagnosis should always be considered in recipients who develop cardiac complications, since negative serological tests do not completely discard the possibility of disease transmission and since good results can be achieved with prompt trypanocidal therapy.

Increased activities of cardiac matrix metalloproteinases matrix metalloproteinase (MMP)-2 and MMP-9 are associated with mortality during the acute phase of experimental Trypanosoma cruzi infection

The strong inflammatory reaction that occurs in the heart during the acute phase of Trypanosoma cruzi infection is modulated by cytokines and chemokines produced by leukocytes and cardiomyocytes. Matrix metalloproteinases (MMPs) have recently emerged as modulators of cardiovascular inflammation. In the present study we investigated the role of MMP-2 and MMP-9 in T. cruzi-induced myocarditis, by use of immunohistochemical analysis, gelatin zymography, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction to analyze the cardiac tissues of T. cruzi-infected C57BL/6 mice. Increased transcripts levels, immunoreactivity, and enzymatic activity for MMP-2 and MMP-9 were observed by day 14 after infection. Mice treated with an MMP inhibitor showed significantly decreased heart inflammation, delayed peak in parasitemia, and improved survival rates, compared with the control group. Reduced levels of cardiac tumor necrosis factor-alpha, interferon-gamma, serum nitrite, and serum nitrate were also observed in the treated group. These results suggest an important role for MMPs in the induction of T. cruzi-induced acute myocarditis.

5-Lipoxygenase is a key determinant of acute myocardial inflammation and mortality during Trypanosoma cruzi infection

This study provides evidence supporting the idea that although inflammatory cells migration to the cardiac tissue is necessary to control the growth of Trypanosoma cruzi, the excessive influx of such cells during acute myocarditis may be deleterious to the host. Production of lipid mediators of inflammation like leukotrienes (LTs) along with cytokines and chemokines largely influences the severity of inflammatory injury in response to tissue parasitism. T cruzi infection in mice deficient in 5-lipoxygenase (5-LO), the enzyme responsible for the synthesis of LTs and other lipid inflammatory mediators, resulted in transiently increased parasitemia, and improved survival rate compared with WT mice. Myocardia from 5-LO(-/-) mice exhibited reduced inflammation, collagen deposition, and migration of CD4(+), CD8(+), and IFN-gamma-producer cells compared with WT littermates. Moreover, decreased amounts of TNF-alpha, IFN-gamma, and nitric oxide synthase were found in the hearts of 5-LO(-/-) mice. Interestingly, despite of early higher parasitic load, 5-LO(-/-) mice survived, and controlled T cruzi infection. These results show that efficient parasite clearance is possible in a context of moderate inflammatory response, as occurred in 5-LO(-/-) mice, in which reduced myocarditis protects the animals during T cruzi infection. (c) 2010 Elsevier Masson SAS. All rights reserved.

Micro-Positron Emission Tomography in the Evaluation of Trypanosoma cruzi-Induced Heart Disease: Comparison with Other Modalities

Noninvasive assessment of cardiac structure and function is essential to understand the natural course of murine infection with Trypanosoma cruzi. Magnetic resonance imaging (MRI) and echocardiography have been used to monitor anatomy and function; positron emission tomography (PET) is ideal for monitoring metabolic events in the myocardium. Mice infected with T. cruzi (Brazil strain) were imaged 15-100 days post infection (dpi). Quantitative (18)F-FDG microPET imaging, MRI and echocardiography were performed and compared. Tracer ((18)F-FDG) uptake was significantly higher in infected mice at all days of infection, from 15 to 100 dpi. Dilatation of the right ventricular chamber was observed by MRI from 30 to 100 dpi in infected mice. Echocardiography revealed significantly reduced ejection fraction by 60 dpi. Combination of these three complementary imaging modalities makes it possible to noninvasively quantify cardiovascular function, morphology, and metabolism from the earliest days of infection through the chronic phase.

Cutting Edge: Nucleotide-Binding Oligomerization Domain 1-Dependent Responses Account for Murine Resistance against Trypanosoma cruzi Infection

An effective innate immune recognition of the intracellular protozoan parasite Trypanosoma cruzi is critical for host resistance against Chagas disease, a severe and chronic illness that affects millions of people in Latin America. In this study, we evaluated the participation of nucleotide-binding oligomerization domain (Nod)like receptor proteins in host response to T cruzi infection and found that Nod1-dependent, but not Nod2-dependent, responses are required for host resistance against infection. Bone marrow-derived macrophages from Nod1(-/-) mice showed an impaired induction of NF-kappa B-dependent products in response to infection and failed to restrict T cruzi infection in presence of IFN-gamma. Despite normal cytokine production in the sera, Nod1(-/-) mice were highly susceptible to T cruzi infection, in a similar manner to MyD88(-/-) and NO synthase 2(-/-) mice. These studies indicate that Nod1-dependent responses account for host resistance against T cruzi infection by mechanisms independent of cytokine production. The Journal of Immunology, 2010, 184: 1148-1152.

The involvement of CD4(+)CD25(+) T cells in the acute phase of Trypanosoma cruzi infection

The infection with Trypanosoma cruzi leads to a vigorous and apparently uncontrolled inflammatory response in the heart. Although the parasites trigger specific immune response, the infection is not completely cleared out, a phenomenon that in other parasitic infections has been attributed to CD4(+)CD25(+) T cells (Tregs). Then, we examined the role of natural Tregs and its signaling through CD25 and GITR in the resistance against infection with T. cruzi. Mice were treated with mAb against CD25 and GITR and the parasitemia, mortality and heart pathology analyzed. First, we demonstrated that CD4(+)CD25(+)GITR(+)Foxp3(+) T cells migrate to the heart of infected mice. The treatment with anti-CD25 or anti-GITR resulted in increased mortality of these infected animals. Moreover, the treatment with anti-GITR enhanced the myocarditis, with increased migration of CD4(+), CD8(+), and CCR5(+) leukocytes, TNF-alpha production, and tissue parasitism, although it did not change the systemic nitric oxide synthesis. These data showed a limited role for CD25 signaling in controlling the inflammatory response during this protozoan infection. Also, the data suggested that signaling through GITR is determinant to control of the heart inflammation, parasite replication, and host resistance against the infection. (C) 2008 Elsevier Masson SAS. All rights reserved.

Regulation of Trypanosoma cruzi-Induced Myocarditis by Programmed Death Cell Receptor

Trypanosoma cruzi infection causes intense myocarditis, leading to cardiomyopathy and severe cardiac dysfunction. Protective adaptive immunity depends on balanced signaling through a T cell receptor and coreceptors expressed on the T cell surface. Such coreceptors can trigger stimulatory or inhibitory signals after binding to their ligands in antigen-presenting cells (APC). T. cruzi modulates the expression of coreceptors in lymphocytes after infection. Deregulated inflammation may be due to unbalanced expression of these molecules. Programmed death cell receptor 1 (PD-1) is a negative T cell coreceptor that has been associated with T cell anergy or exhaustion and persistent intracellular infections. We aimed to study the role of PD-1 during T. cruzi-induced acute myocarditis in mice. Cytometry assays showed that PD-1 and its ligands are strongly upregulated in lymphocytes and APC in response to T. cruzi infection in vivo and in vitro. Lymphocytes infiltrating the myocardium exhibited high levels of expression of these molecules. An increased cardiac inflammatory response was found in mice treated with blocking antibodies against PD-1, PD-L1, and to a lesser extent, PD-L2, compared to that found in mice treated with rat IgG. Similar results in PD-1(-/-) mice were obtained. Moreover, the PD-1 blockade/deficiency led to reduced parasitemia and tissue parasitism but increased mortality. These results suggest the participation of a PD-1 signaling pathway in the control of acute myocarditis induced by T. cruzi and provide additional insight into the regulatory mechanisms in the pathogenesis of Chagas` disease.

Phylogenetic relationships of Trypanosoma chelodina and Trypanosoma binneyi from Australian tortoises and platypuses inferred from small subunit rRNA analyses

Trypanosome infections are often difficult to detect by conventional microscopy and their pleomorphy often confounds differential diagnosis. Molecular techniques are now being used to diagnose infections and to determine phylogenetic relationships between species. Complete small subunit rRNA gene sequences were determined for isolates of Trypanosoma chelodina from the Brisbane River tortoise (Emydura signata), the saw-shelled tortoise (Elseya latisternum), and the eastern snake-necked tortoise (Chelodina longicollis) from southeast Queensland, Australia. Partial sequence data were also obtained for T. binneyi from a platypus (Ornithorhynchus anatinus) from Tasmania. Phylogenetic relationships between T. chelodina, T. binneyi and other species were examined by maximum parsimony and likelihood methods. The Australian tortoise and platypus trypanosomes did not exhibit any close phylogenetic relationships with those of mammals, reptiles or amphibians, but were closely related to each other, and to fish trypanosomes. This contra-indicates their co-evolution with their vertebrate hosts but does not exclude co-evolution with different groups of invertebrate vectors, notably insects and leeches.

Experiências sôbre a transmissão do Trypanosoma cruzi por sanguessugas e de tripanosomas de vertebrados de sangue frio por triatomíneos

Observou-se que o Trypanosoma cruzi não se multiplica na sanguessuga (Haementeria lutzi Pinto); os tripanosomas sugados degeneram após algum tempo; outros permanecem aparentemente normais, porém 48 horas após a ingestão infectante acabam morrendo. Observou-se ainda que os tripanosomas parasitas da rã (T. rotatorium e T. leptodactyli) bem como o T. hogei, parasita da serpente Rachidelus brazili, não se multiplicam no intestino dos triatomíneos. O mais resistente (o T. leptodactyli), permanece vivo até 72 horas após a ingestão infectante, porém as outras duas espécies (T. rotatorium e T. hogei) não resistem mais de 24 horas após serem sugadas pelos triatomíneos.

Esterilidad individual en Rhodnius prolixus Stal. tratados con metepa (oxido de tris (1-(2 metil) aziridinil) fosfuro), y accion del mismo sobre Trypanosoma cruzi

Se analizan los factores que interfieren en la esterilidad inducida químicamente en R. Prolixus mediante aplicaciones tópicas en distintas dosis de metepa. Se sugiere profundizar el estudio de la susceptibilidad individual para conocer la composición de la población frente al quimioesterilizante y la probable aparición de resistencia. Se investiga además la acción del metepa sobre T. cruzi en triatominos infectados experimentalmente, obteniéndose resultados negativos.

Recovery of Trypanosoma forattinii Coutinho and Pattoli from a Trinidadian rodent

Recovery of Trypanosoma forattinii from natural infected Oryzomys capito velutinus from Trinidad, is reported. Negative results were obtained with attempts to infect experimentally, several laboratories animals, silvatyc rodents of the same ecological area and several species of triatomids bugs. Positive results were obtained only by using O. capito velutinus born in laboratory.

Novo encontro do Trypanosoma (Megatrypanum) freitasi, parasita do gambá

Relata-se um novo encontro do Trypanosoma (Megatrypanum) freitasi, raro tripanosomatídeo encontrado no sangue de marsupiais, do gênero Didelphis. Salientam-se a baixa e irregular parasitemia observada, as dificuldades no isolamento, bem como, o concomitante achado do T. cruzi.

Nota sobre a infecção natural de Calomys expulsus, Lund, 1841 (Cricetidae-Rodentia) pelo Trypanosoma cruzi

Foi isolada uma amostra de T. cruzi do roedor silvestre, Calomys expulsus, Lund, 1841, capturado no norte do município de Formosa, Goiás, através de inoculações em animais de laboratório, e subseqüente xenodiagnósticos com R. neglectus, T. infestans e P. megistus. A amostra de T. cruzi apresentou patogenicidade muito baixa para os animais inoculados, mas conferiu resistência a reinjecções a cêpa Y de origem humana. As jornias sanguícolas tiveram um comprimento total médio de 21.8 µ e o índice nuclear foi 1.15.

Prevalência da infecção por Trypanosoma cruzi, em 1975, em dois bancos de sangue de Londrina, Paraná, Brasil

Foi realizado inquérito sobre a positividade de reações sorológicas para o diagnóstico de tripanossomíase americana, em 4.500 candidatos a doadores não selecionados, atendidos em 1975, em dois bancos de sangue de Londrina, Paraná, Brasil. Observou-se resultado positivo da reação de fixação do complemento em 299 (7,9%) dos 3.774 candidatos a doadores atendidos no Banco de Sangue do Hospital Universitário (indivíduos residentes predominantemente na zona rural), tendo também sido positivos os resultados da reação de fixação do complemento e do teste de imunofluorescência indireta em 38 (5,2%) dos 726 candidatos a doadores atendidos no Instituto de Hematologia e Hemoterapia (indivíduos residentes predominantemente na zona urbana). Na casuística global a positividade observada foi de 7,4%. Dentre os 337 candidatos a doadores com reação sorológica positiva, 97 (28,7%) informaram ter doado sangue anteriormente, em outro local, 71 (21,0%) dos quais em período prévio menor que um ano, e 42 (12,4%) em período prévio menor que seis meses, em relação à data do nosso exame. Comparando os dados obtidos nesta avaliação com os de inquéritos semelhantes efetuados em 1958 em bancos de sangue deste município, concluiu-se que não houve, nesse período, alteração significativa nos índices de infecção por Trypanosoma cruzi em Londrina. Chamam a atenção para a discrepância entre o reduzido número de casos de doença de Chagas pós-transfusional relatados na literatura e os altos índices de positividade de reações sorológicas para o diagnóstico de tripanossomíase americana registrados em bancos de sangue de diversas regiões do Brasil. Foi ressaltada, a importância de exigir-se maior rigor e parcimônia nas indicações de transfusões de sangue, e dada ênfase às normas que devem ser respeitadas quando o uso desse recurso terapêutico tiver indicação formal.

Sobre o encontro do Trypanosoma (Herpetosoma) renjifoi Deane 1961, infectando Proechimys longicaudatus (Rodentia-Echimyidae)

É relatado o encontro do roedor Proechimys longicaudatus, capturado na Fazenda Água Limpa, Brasília-DF (Brasil), naturalmente infectado pelo Trypanosoma (Herpetosoma) renjifoi. Este é o primeiro relato do T. (H.) renjifoi na região do Brasil Central.