Transplantation for Chagas’ disease: an overview of immunosuppression and reactivation in the last two decades

Bacal, Fernando; Silva, Christiano Pereira; Pires, Philippe Vieira; Mangini, Sandrigo; Fiorelli, Alfredo Inácio; Stolf, Noedir; Bocchi, Edimar Alcides

doi:10.1111/j.1399-0012.2009.01202.x

Cited by 82 publications

(66 citation statements)

References 34 publications

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“…Sin embargo, el mayor impacto se observa en parásitos que por su naturaleza intracelular, o su acción directa interna sobre órganos vitales, son profundamente afectados por cualquier alteración en la inmunidad celular, blanco fundamental de la inmunosupresión (Ferreira & Borges 2002, Dedet & Pratlong 2005. Tal es el caso de los tripanosomas del grupo Salivaria (africanos) (Uzonna et al 1998), (Trypanosoma cruzi (Krettli 1977, Sztein & Kierszenbaum 1993, Bacal et al 2010, Leishmania spp. (Oliveira et al 2008), Toxoplasma gondii (Abedalthagafi et al 2009, García et al 2010, Soléne et al 2010 y Plasmodium falciparum (Grimwade et al 2004).…”

Section: Resultsunclassified

Efecto inmunosupresor de la infección por <i>Trypanosoma musculi</i> (Mastigophora: Trypanosomatidae) en la toxoplasmosis experimental

Piccolo-Johanning

Kellerman-Guterman

Valerio-Campos

et al. 2013

RBT

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Immunosuppressor effect of Trypanosoma musculi (Mastigophora: Trypanosomatidae) on experimental toxoplasmosis. The immunosuppression caused by species of the gender Trypanosoma has been widely documented. The influence over experimental infections with Toxoplasma gondii is evident when using Trypanosoma lewisi, a natural parasite of white rats. We decided to test the effect of Trypanosoma musculi from mice, an organism with very similar biological characteristics to T. lewisi, to see if this trypanosomatid could induce a similar effect. Four groups of Swiss mice were inoculated with T. musculi previously to infection with T. gondii, and we determined the survival of the animals, as well as the number of cysts developed in the brain of survivors. We isolated and tested different strains of T. gondii from different sources. In a first experiment, the animals were previously inoculated with T. musculi at different times prior to the infection with Toxoplasma; this allowed us to determine that the immunosuppression process resulted more evident when T. musculi inoculation was made four days before. In a second experiment, we used different inoculi dose and found that it did not influenced the process. Furthermore, the results were negative when evaluating if the amount of the inoculated trypomastigote influenced the process. In order to demonstrate if there were differences in the immnosuppressive effect, related to Toxoplasma strains, groups of mice were inoculated with brain cysts of TFC, TLP, TLW and TBT strains. Excluding the TLP strain, that resulted to be very pathogenic regardless the previous inoculation with T. lewisi, the other strains kept the same pattern of immunosuppression in mice, whose survival time was shorter as the presence of cysts in the brain was higher. These observations were in agreement with an experimental immunosuppression model, associated with immunosuppressive diseases, specially cancer and AIDS. Rev. Biol. Trop. 61 (2): 981-990. Epub 2013 June 01.

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Section: Resultsunclassified

Efecto inmunosupresor de la infección por <i>Trypanosoma musculi</i> (Mastigophora: Trypanosomatidae) en la toxoplasmosis experimental

Piccolo-Johanning

Kellerman-Guterman

Valerio-Campos

et al. 2013

RBT

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“…Los triángulos indican el periodo del tratamiento y los días en los que se tomaron muestras después del tratamiento, correspondientes a 270, 480 y 540 días después del trasplante, respectivamente, se señalan con un círculo. de tratamiento indicada para los pacientes con cardiomiopatía chagásica crónica (11,(27)(28)(29).…”

Section: Discussionunclassified

“…Seguimiento de paciente con enfermedad de Chagas y trasplante polimerasa (PCR) en sangre o tejidos, siendo el xenodiagnóstico y el hemocultivo los menos utilizados por su menor sensibilidad y tiempo requerido no menor de 30 días para obtener el resultado (11). El estudio histopatológico es uno de los métodos más utilizados para detectar T. cruzi en lesiones del tejido cardiaco y otros.…”

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Seguimiento de paciente con enfermedad de Chagas y trasplante de corazón mediante las PCR S35-S36 y TcH2AF-R

et al. 2011

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Introducción. La cardiomiopatía es la forma clínica más común de la enfermedad de Chagas en Colombia, siendo el trasplante una opción para su tratamiento. Debido al riesgo de reactivación de la infección posterior al trasplante, es prioritario vigilar el comportamiento del parásito. Objetivo. Presentar el caso de un paciente con cardiopatía chagásica dilatada y falla cardiaca, a quien se le practicó trasplante de corazón y se le hizo seguimiento mediante PCR, análisis histopatológicos y ecocardiográficos. Materiales y métodos. Se tomaron muestras de sangre antes de la intervención y después de ella y de biopsias endomiocárdicas posteriores al trasplante. El ADN extraído fue amplificado con los iniciadores TcH2AF-R y S35-S36. La parasitemia se examinó mediante la técnica de microhematocrito. Se practicaron estudios histopatológicos para determinar la presencia del parásito o el rechazo del trasplante y, ecocardiográficos, para evaluar la función cardiaca. Resultados. De las muestras de sangre tomadas a los 83 y 48 días previos al trasplante, la última fue positiva por la PCR S35-S36. Hasta el segundo mes después del trasplante, ambas PCR fueron negativas. Al tercer mes después del trasplante, ambas PCR fueron positivas, por lo cual se inició tratamiento con nifurtimox. Tras 35 días de haberse iniciado el tratamiento, ambas pruebas presentaron resultados negativos, al igual que las tomadas a los 0, 3, 10 y 12 meses posteriores. Los resultados de la histopatología, del microhematocrito y de las PCR de las biopsias, fueron negativos en todas las fechas. Conclusiones. Las PCR permitieron sospechar la reactivación de la infección en el paciente, se le administró el tratamiento y posterioremente las pruebas se tornaron negativas. La evolución clínica del paciente ha sido favorable.Palabras clave: Trypanosoma cruzi, enfermedad de Chagas, trasplante, reacción en cadena de la polimerasa (PCR), ecocardiografía, cardiomiopatía dilatada. Using S35-S36 and TcH2AF-R primer-based PCR tests to follow-up a Chagas' disease patient who had undergone a heart transplantIntroduction. Cardiomyopathy is the most common clinical form of Chagas' disease in Colombia, and one treatment option is a heart transplant. Tracking the behavior of the Chagas' parasite, Trypanosoma cruzi, is a priority due to the risk of post-transplant reactivation of the infection. Objective. A case is presented of a patient who had suffered from dilated chagasic cardiopathy and cardiac failure, and had subsequently undergone heart transplant. The case was monitored by PCR, histopathological and echocardiographic examinations. Materials and methods. Blood samples were drawn before and after the transplant, and post-transplant endomyocardial biopsies were taken. The extracted DNA was amplified with the TcH2AF-R and S35-S36 primers. Parasitemia was examined by the microhematocrit test. In addition, histopathological studies determined the parasite presence and transplant rejection status. Echocardiograms were administered to evaluate cardiac function. Results. Of th...

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“…Thus, an inducer effect of BZL in patients cannot be ruled out because the time of treatment is more extended than in our experimental approach. Drug-drug interactions could be particularly important in chagasic patients under immunosuppressant treatment with cyclosporine, corticosteroids, and azathioprine for heart or kidney transplantation (42,43) or in HIV patients infected with T. cruzi and receiving antiretrovirals (44,45).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats

Perdomo

Rigalli

Villanueva

et al. 2013

Antimicrob Agents Chemother

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The effect of antichagasic benznidazole (BZL; 100 mg/kg body weight/day, 3 consecutive days, intraperitoneally) on biotransformation systems and ABC transporters was evaluated in rats. Expression of cytochrome P-450 (CYP3A), UDP-glucuronosyltransferase (UGT1A), glutathione S-transferases (alpha glutathione S-transferase [GST-␣], GST-, and GST-), multidrug-resistance-associated protein 2 (Mrp2), and P glycoprotein (P-gp) in liver, small intestine, and kidney was estimated by Western blotting. Increases in hepatic CYP3A (30%) and GST-(40%) and in intestinal GST-␣ (72% in jejunum and 136% in ileum) were detected. Significant increases in Mrp2 (300%) and P-gp (500%) proteins in liver from BZL-treated rats were observed without changes in kidney. P-gp and Mrp2 were also increased by BZL in jejunum (170% and 120%, respectively). In ileum, only P-gp was increased by BZL (50%). The activities of GST, P-gp, and Mrp2 correlated well with the upregulation of proteins in liver and jejunum. Plasma decay of a test dose of BZL (5 mg/kg body weight) administered intraduodenally was faster (295%) and the area under the concentration-time curve (AUC) was lower (41%) for BZL-pretreated rats than for controls. The biliary excretion of BZL was higher (60%) in the BZL group, and urinary excretion of BZL did not show differences between groups. The amount of absorbed BZL in intestinal sacs was lower (25%) in pretreated rats than in controls. In conclusion, induction of biotransformation enzymes and/or transporters by BZL could increase the clearance and/or decrease the intestinal absorption of coadministered drugs that are substrates of these systems, including BZL itself.

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Transplantation for Chagas’ disease: an overview of immunosuppression and reactivation in the last two decades

Cited by 82 publications

References 34 publications

Efecto inmunosupresor de la infección por <i>Trypanosoma musculi</i> (Mastigophora: Trypanosomatidae) en la toxoplasmosis experimental

Efecto inmunosupresor de la infección por <i>Trypanosoma musculi</i> (Mastigophora: Trypanosomatidae) en la toxoplasmosis experimental

Seguimiento de paciente con enfermedad de Chagas y trasplante de corazón mediante las PCR S35-S36 y TcH2AF-R

Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats

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