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Maria Terezinha Bahia - One of the best experts on this subject based on the ideXlab platform.
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outcome of e1224 Benznidazole combination treatment for infection with a multidrug resistant trypanosoma cruzi strain in mice
2018Co-Authors: Lívia De Figueiredo Diniz, Ivo Santana Caldas, Isabela Ribeiro, Ana Lia Mazzeti, Maria Terezinha BahiaAbstract:Combination therapy has been proposed as an alternative therapeutic approach for the treatment of Chagas disease. In this study, we evaluated the effect of treatment with Benznidazole combined with E1224 (ravuconazole prodrug) in an experimental murine model of acute infection. The first set of experiments assessed the range of E1224 doses required to induce parasitological cure using Trypanosoma cruzi strains with different susceptibilities to Benznidazole (Y and Colombian). All E1224 doses were effective in suppressing the parasitemia and preventing death; however, parasitological cure was observed only in mice infected with Y strain. Considering these results, we evaluated the effect of combined treatment against Colombian, a multidrug-resistant T. cruzi strain. After exclusion of antagonistic effects using in vitro assays, infected mice were treated with E1224 and Benznidazole in monotherapy or in combination at day 4 or 10 postinoculation. All treatments were well tolerated and effective in suppressing parasitemia; however, parasitological and PCR assays indicated no cure among mice treated with monotherapies. Intriguingly, the outcome of combination therapy was dependent on treatment onset. Early treatment using optimal doses of E1224-Benznidazole induced a 100% cure rate, but this association could not eliminate a well-established infection. The beneficial effect of combination therapy was evidenced by further reductions of the patent parasitemia period in the group receiving combined therapy compared with monotherapies. Our results demonstrated a positive interaction between E1224 and Benznidazole against murine T. cruzi infection using a multidrug-resistant strain and highlighted the importance of a stringent experimental model in the evaluation of new therapies.
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Benznidazole itraconazole combination treatment enhances anti trypanosoma cruzi activity in experimental chagas disease
2015Co-Authors: Tassiane Assíria Fontes Martins, Isabel Mayer De Andrade, Lívia De Figueiredo Diniz, Ivo Santana Caldas, Isabela Ribeiro, Álvaro Fernando Da Silva Do Nascimento, Ana Lia Mazzeti, Sergio Caldas, Maria Terezinha BahiaAbstract:The nitroheterocyclic drugs nifurtimox and Benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity. Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy. In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease. The curative action of Benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain. The activities of the Benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug. The administration of Benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone. Here, there was a significant reduction of the number of treatment days (number of doses) necessary to induce parasitemia suppression with the Benznidazole/itraconazole combination, as compared to each compound administered alone. These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone. Moreover, Benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice. These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease.
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Benznidazole and posaconazole in experimental chagas disease positive interaction in concomitant and sequential treatments
2013Co-Authors: Lívia De Figueiredo Diniz, Isabel Mayer De Andrade, Tassiane Assíria Fontes Martins, Ivo Santana Caldas, André Talvani, Isabela Ribeiro, Julio A Urbina, Ana Lia Mazzeti, Maria Terezinha BahiaAbstract:Background: Current chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with frequent side effects that can lead to treatment discontinuation. Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. We evaluated the efficacy of posaconazole in combination with Benznidazole on Trypanosoma cruzi infection in vivo. Methods and Findings: Benznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. Using a rapid treatment protocol for 7 days, the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone, with the effects most evident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk) of Benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses, indicating synergistic activity. Finally, sequential therapy experiments were carried out with Benznidazole or posaconazole over a short interval (10 days), followed by the second drug administered for the same period of time. It was found that the sequence of Benznidazole (100 mpk) followed by posaconazole (20 mpk) provided cure rates comparable to those obtained with the full (20 days) treatments with either drug alone, and no cure was observed for the short treatments with drugs given alone. Conclusions: Our data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds, and showed that combinations of Benznidazole with posaconazole have a positive interaction in murine models of Chagas disease.
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Chemical structure of fexinidazole and Benznidazole.
2013Co-Authors: Maria Terezinha Bahia, Els Torreele, Bernadette Bourdin Trunz, Isabel Mayer De Andrade, Tassiane Assíria Fontes Martins, Lívia De Figueiredo Diniz, Ivo Santana Caldas, André Talvani, Álvaro Fernando Da Silva Do Nascimento, Isabela RibeiroAbstract:Chemical structure of fexinidazole and Benznidazole.
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in vivo susceptibility to Benznidazole of trypanosoma cruzi strains from the western brazilian amazon
2013Co-Authors: Ana Paula Margioto Teston, Silvana Marques Araújo, Mônica Lúcia Gomes, Maria Terezinha Bahia, Wuelton Marcelo Monteiro, Daniele Dos Reis, Gleison Daion Piovezana Bossolani, Maria Das Gracas Vale Barbosa, Max Jean Ornelas ToledoAbstract:Objective To assess the susceptibility of Trypanosoma cruzi strains from Amazon to Benznidazole. Methods We studied 23 strains of T. cruzi obtained from humans in the acute phase of Chagas disease, triatomines and marsupials in the state of Amazonas and from chronic patients and triatomines in the state of Parana, Brazil. The strains were classified as TcI (6), TcII (4) and TcIV (13). For each strain, 20 Swiss mice were inoculated: 10 were treated orally with Benznidazole 100 mg/kg/day (TBZ group) for 20 consecutive days and 10 comprised the untreated control group (NT). Fresh blood examination, haemoculture (HC), PCR, and ELISA were used to monitor the cure. Results The overall cure rate was 60.5% (109/180 mice) and varied widely among strains. The strains were classified as resistant, partially resistant or susceptible to Benznidazole, irrespective of discrete typing units (DTUs), geographical origin or host. However, the TcI strains from Amazonas were significantly (P = 0.028) more sensitive to Benznidazole than the TcI strains from Parana. The number of parasitological, molecular and serological parameters that were significantly reduced by Benznidazole treatment also varied among the DTUs; the TBZ group of mice inoculated with TcIV strains showed more reductions (8/9) than those with TcI and TcII strains. Conclusions Benznidazole resistance was observed among natural populations of the parasite in the Amazon, even in those never exposed to the drug. Objective Evaluer la sensibilite de souches de Trypanosoma cruzi de l’Amazonie au Benznidazole. Methodes Nous avons etudie 23 souches de T. cruzi provenant de l'homme dans la phase aigue de la maladie de Chagas, de triatomes et de marsupiaux dans l'Etat d'Amazonas, et de malades chroniques et triatomes de l’Etat du Parana, au Bresil. Les souches ont ete classees comme TcI (6), TcII (4) et TcIV (13). Pour chaque souche, 20 souris suisses ont ete inoculees: 10 ont ete traitees par voie orale avec du Benznidazole a 100 mg/kg/jour (groupe TBZ) pendant 20 jours consecutifs et 10 formaient le groupe temoin non traite (NT). L'examen du sang frais, l'hemoculture, la PCR et l’ELISA ont ete utilises pour suivre le traitement. Resultats Le taux global de guerison etait de 60,5% (109/180 souris) et variait considerablement entre les souches. Les souches ont ete classees comme resistantes, partiellement resistantes ou sensibles au Benznidazole, quelle que soit la DTU, la provenance geographique ou l'hote. Cependant, les souches de TcI provenant d'Amazonas etaient significativement (P = 0,028) plus sensibles au Benznidazole que les souches TcI de Parana. Le nombre de parametres parasitologiques, serologiques et moleculaires qui ont ete considerablement reduits par le traitement au Benznidazole variait egalement selon les DTU; le groupe TBZ des souris inoculees avec des souches TcIV a revele plus de reductions (8/9) que celui de souris inoculees avec des souches TcI et TcII. Conclusions La resistance au Benznidazole a ete observee dans les populations naturelles du parasite dans l'Amazonie, meme dans celles qui n'ont jamais ete exposees a ce medicament. Objetivo Evaluar la susceptibilidad de cepas de Trypanosoma cruzi del Amazonas al benznidazol. Metodos Hemos estudiado 23 cepas de T. cruzi obtenidas de humanos en la fase aguda de la enfermedad de Chagas, triatominos y marsupiales en el Estado del Amazonas, y de pacientes cronicos y triatominos en el Estado de Parana, Brasil. Las cepas se clasificaron como TcI (6), TcII (4) y TcIV (13). Con cada cepa se inocularon 20 ratones Suizos: 10 fueron tratados oralmente con benznidazol 100 mg/kg/dia (grupo TBZ) durante 20 dias consecutivos y 10 conformaban el grupo control sin tratar (ST). Para monitorizar la curacion, se utilizaron un examen de sangre fresca, hemocultivo, PCR y ELISA. Resultados La tasa total de curacion fue del 60.5% (109/180 ratones) y vario ampliamente entre las cepas. Las cepas se clasificaron como resistentes, parcialmente resistentes o susceptibles al benznidazol, independientemente del grupo de tratamiento, origen geografico u hospedero. Sin embargo, las cepas TcI del Amazonas eran significativamente (P = 0.028) mas susceptibles al benznidazol que las cepas TcI de Parana. El numero de parametros parasitologicos, moleculares y serologicos que se reducian significativamente con el tratamiento con benznidazol tambien variaban entre los grupos de tratamiento; en el grupo TBZ los ratones inoculados con las cepas TcIV mostraban una mayor reduccion (8/9) que aquellos inoculados con las cepas TcI y TcII. Conclusiones Se observo Resistencia al Benznidazol entre poblaciones naturales del parasito en el Amazonas, incluso entre aquellos que no habian estado previamente expuestos al medicamento.
Rodolfo Viotti - One of the best experts on this subject based on the ideXlab platform.
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Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study.
2017Co-Authors: María G. Álvarez, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Rodolfo ViottiAbstract:Abstract Since the decline in new cases of infection by insect/vector, congenital Chagas disease has become more relevant in the transmission of Chagas disease. Treatment with Benznidazole significantly reduces the parasitemia, which constitutes an important factor linked to vertical transmission. The objective of this study was to evaluate whether treatment with Benznidazole previously administered to women of childbearing age can prevent or reduce the incidence of new cases of congenital Chagas disease. An historical cohort study that included all women in reproductive age (15–45 years) assisted in our center was designed. We included 67 mothers with chronic Chagas disease; 35 women had not been treated prior to pregnancy, 15 had been treated prior to pregnancy and 17 gave birth prior and after treatment with Benznidazole. Eight mothers gave birth to 16 children with congenital Chagas disease (8/67, 12%). The prevalence of congenital Chagas was 16/114 (14%) children born to untreated mothers and 0/42 (0%) children born to Benznidazole- treated mothers, p = 0.01. No significant differences were observed in clinical, serologic, epidemiological or socioeconomic baseline variables between mothers with and without children born with congenital Chagas. A 32% conversion rate to negative serology was observed in Benznidazole-treated women after long-term follow up. Antiparasitic treatment administered to women in reproductive age can prevent the occurrence of congenital Chagas disease.
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seronegative conversion after incomplete Benznidazole treatment in chronic chagas disease
2012Co-Authors: María G. Álvarez, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Rodolfo ViottiAbstract:In 12–18% of adult patients, treatment with Benznidazole for chronic Chagas disease has to be discontinued because of side-effects. We identified and analysed a cohort of 81 adult patients with three positive tests for Trypanosoma cruzi infection and serological monitoring following incomplete treatment with Benznidazole for a median of 10 days. Twenty percent of these patients (16/81) met the criteria of cure, showing that the optimal schedule of Benznidazole administration remains to be determined.
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side effects of Benznidazole as treatment in chronic chagas disease fears and realities
2009Co-Authors: Rodolfo Viotti, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Maria Gabriela Alvarez, Alejandro ArmentiAbstract:Chagas disease is caused by a parasite, Trypanosoma cruzi, transmitted primarily by a triatomine insect and affects approximately 8 million people in Latin American countries. The principal aim of the management of the disease is to avoid the development of cardiomyopathy and transmission by blood transfusion, congenital and organ transplants. Currently, Benznidazole is the only etiological treatment commercially available for the disease until new and better drugs can be developed and tested. Benznidazole has been used even though it does not have all the conditions of an ideal drug. The efficacy and tolerance of Benznidazole is inversely related to the age of the patient, while its side effects are more frequent in elderly patients. The side effects are systematically evaluated only in controlled studies designed for that purpose. However, the true clinical impact of the side effects could be different, considering that the treatment is for a short duration (between 30 and 60 days) and only carried out ...
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long term cardiac outcomes of treating chronic chagas disease with Benznidazole versus no treatment
2006Co-Authors: Rodolfo Viotti, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Maria Gabriela Alvarez, Miriam Postan, Alejandro ArmentiAbstract:The authors assigned alternate patients with chronic Chagas disease to treatment with Benznidazole or to no treatment and followed them for a mean of approximately 10 years. The patients had no evi...
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long term cardiac outcomes of treating chronic chagas disease with Benznidazole versus no treatment a nonrandomized trial
2006Co-Authors: Rodolfo Viotti, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Maria Gabriela Alvarez, Miriam Postan, Alejandro ArmentiAbstract:Background: Benznidazole is effective for treating acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain. Objective: To compare long-term outcomes of patients with nonacute Chagas disease treated with Benznidazole versus outcomes of those who did not receive treatment. Design: Clinical trial with unblinded, nonrandom assignment of patients to intervention or control groups. Setting: Chagas disease center in Buenos Aires, Argentina. Patients: 566 patients 30 to 50 years of age with 3 positive results on serologic tests and without heart failure. Measurements: The primary outcome was disease progression, defined as a change to a more advanced Kuschnir group or death. Secondary outcomes included new abnormalities on electrocardiography and serologic reactivity. Intervention: Oral Benznidazole, 5 mg/kg of body weight per day for 30 days (283 patients), or no treatment (283 patients). Results: Fewer treated patients had progression of disease (12 of 283 [4%] vs. 40 of 283 [14%]; adjusted hazard ratio, 0.24 [95% Cl, 0.10 to 0.59]; P = 0.002) or developed abnormalities on electrocardiography (15 of 283 [5%] vs. 45 of 283 [16%]; adjusted hazard ratio, 0.27 [Cl, 0.13 to 0.57]; P= 0.001) compared with untreated patients. Left ventricular ejection fraction (hazard ratio, 0.97 [Cl, 0.94 to 0.99]; P < 0.002) and left ventricular diastolic diameter (hazard ratio, 2.45 [Cl, 1.53 to 3.95]; P< 0.001) were also associated with disease progression. Conversion to negative results on serologic testing was more frequent in treated patients than in untreated patients (32 of 218 [15%] vs. 12 of 212 [6%]; adjusted hazard ratio, 2.1 [Cl, 1.06 to 4.06]; P = 0.034). Limitations: Nonrandom, unblinded treatment assignment was used, and follow-up data were missing for 20% of patients. Loss to follow-up was more common among patients who were less sick. Two uncontrolled interim analyses were conducted. Conclusions: Compared with no treatment, Benznidazole treatment was associated with reduced progression of Chagas disease and increased negative seroconversion for patients presenting with nonacute disease and no heart failure. These observations indicate that a randomized, controlled trial should now be conducted.
Maria Helena Sarragiotto - One of the best experts on this subject based on the ideXlab platform.
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in vitro and in vivo trypanocidal synergistic activity of n butyl 1 4 dimethylamino phenyl 1 2 3 4 tetrahydro β carboline 3 carboxamide associated with Benznidazole
2012Co-Authors: Rodrigo Hinojosa Valdez, Edilson Nobuyoshi Kaneshima, Lilian Tatiani Dusman Tonin, Tânia Uedanakamura, Sueli De Oliveira Silva, Benedito Prado Dias Filho, Sueli Fumie Yamadaogatta, Lucy Megumi Yamauchi, Maria Helena SarragiottoAbstract:American trypanosomiasis, or Chagas' disease, is caused by Trypanosoma cruzi and affects around 15 million people throughout the American continent. The available treatment is based on two nitroheterocyclic drugs, nifurtimox and Benznidazole, both only partially effective and toxic. In this context, new drugs must be found. In our previous work, the tetrahydro-β-carboline compound N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide, named C4, showed a potent in vitro trypanocidal effect. The goal of this study was to evaluate the in vitro and in vivo trypanocidal effects of the compound C4 associated with other drugs (Benznidazole, ketoconazole, and amphotericin B). For this, we used the checkerboard technique to analyze the effect of combinations of C4 reference drugs. C4 was assayed in a murine model alone as well as in association with Benznidazole. We also evaluated the parasitemia, mortality, weight, and presence of amastigote nests in cardiac tissue. A synergic effect of C4 plus Benznidazole against epimastigote and trypomastigote forms was observed in vitro, and in the murine model, we observed a substantial reduction in parasitemia levels and lowered mortality rates. These findings encourage supplementary investigations of carboline compounds as potential new trypanocidal drugs.
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comparative study of the trypanocidal activity of the methyl 1 nitrophenyl 1 2 3 4 9h tetrahydro β carboline 3 carboxylate derivatives and Benznidazole using theoretical calculations and cyclic voltammetry
2009Co-Authors: Lilian Tatiani Dusman Tonin, Celso Vataru Nakamura, Valeria Aquilino Barbosa, Cleverson C Bocca, Erika R F Ramos, Willian Ferreira Da Costa, Ernani A Basso, Tânia Ueda Nakamura, Maria Helena SarragiottoAbstract:The cis and trans isomers of methyl 1-(m-nitro)phenyl and 1-(p-nitro)phenyl-1,2,3,4-tetrahydro-9H-beta-carboline-3-carboxylates (compounds 3a,b, 4a and b) were synthesized and evaluated in vitro against epimastigote forms of Trypanosoma cruzi. Among all of the evaluated tetrahydro-beta-carboline derivatives, the compound trans-methyl 1-(m-nitro)phenyl-1,2,3,4-9H-tetrahydro-beta-carboline-3-carboxylate (3b) was found to exhibit significant trypanocidal activity (IC(50)=22.2 microM). Theoretical studies of molecular conformations and electronic properties for the synthesized compounds and Benznidazole, as well as, the cyclic voltammetric (CV) behaviors' determination were performed. A comparative study of the trypanocidal activity of the nitrophenyl-tetrahydro-beta-carbolines derivatives and Benznidazole, using the results of theoretical calculations and of the cyclic voltammetry experiments, is presented.
Graciela Bertocchi - One of the best experts on this subject based on the ideXlab platform.
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Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study.
2017Co-Authors: María G. Álvarez, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Rodolfo ViottiAbstract:Abstract Since the decline in new cases of infection by insect/vector, congenital Chagas disease has become more relevant in the transmission of Chagas disease. Treatment with Benznidazole significantly reduces the parasitemia, which constitutes an important factor linked to vertical transmission. The objective of this study was to evaluate whether treatment with Benznidazole previously administered to women of childbearing age can prevent or reduce the incidence of new cases of congenital Chagas disease. An historical cohort study that included all women in reproductive age (15–45 years) assisted in our center was designed. We included 67 mothers with chronic Chagas disease; 35 women had not been treated prior to pregnancy, 15 had been treated prior to pregnancy and 17 gave birth prior and after treatment with Benznidazole. Eight mothers gave birth to 16 children with congenital Chagas disease (8/67, 12%). The prevalence of congenital Chagas was 16/114 (14%) children born to untreated mothers and 0/42 (0%) children born to Benznidazole- treated mothers, p = 0.01. No significant differences were observed in clinical, serologic, epidemiological or socioeconomic baseline variables between mothers with and without children born with congenital Chagas. A 32% conversion rate to negative serology was observed in Benznidazole-treated women after long-term follow up. Antiparasitic treatment administered to women in reproductive age can prevent the occurrence of congenital Chagas disease.
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new scheme of intermittent Benznidazole administration in patients chronically infected with trypanosoma cruzi a pilot short term follow up study with adult patients
2016Co-Authors: Maria Gabriela Alvarez, Bruno Lococo, Graciela Bertocchi, Alejandro G Schijman, Yolanda Hernandez, Marisa M Fernandez, Juan Carlos Ramirez, Carolina Cura, Constanza Lopez Albizu, Marcelo AbrilAbstract:There is a clinical need to test new schemes of Benznidazole administration that are expected to be at least as effective as the current therapeutic scheme but safer. This study assessed a new scheme of Benznidazole administration in chronic Chagas disease patients. A pilot study with intermittent doses of Benznidazole at 5 mg/kg/day in two daily doses every 5 days for a total of 60 days was designed. The main criterion of response was the comparison of quantitative PCR (qPCR) findings prior to and 1 week after the end of treatment. The safety profile was assessed by the rate of suspensions and severity of adverse effects. Twenty patients were analyzed for safety, while qPCR was tested for 17 of them. The average age was 43 ± 7.9 years; 55% were female. Sixty-five percent of treated subjects showed detectable qPCR results prior to treatment of 1.45 (0.63 to 2.81) and 2.1 (1.18 to 2.78) parasitic equivalents per milliliter of blood (par.eq/ml) for kinetoplastic DNA (kDNA) qPCR and nuclear repetitive sequence satellite DNA (SatDNA) qPCR, respectively. One patient showed detectable PCR at the end of treatment (1/17), corresponding to 6% treatment failure, compared with 11/17 (65%) patients pretreatment (P = 0.01). Adverse effects were present in 10/20 (50%) patients, but in only one case was treatment suspended. Eight patients showed mild adverse effects, whereas moderate reactions with increased liver enzymes were observed in two patients. The main accomplishment of this pilot study is the promising low rate of treatment suspension. Intermittent administration of Benznidazole emerges a new potential therapeutic scheme, the efficacy of which should be confirmed by long-term assessment posttreatment.
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seronegative conversion after incomplete Benznidazole treatment in chronic chagas disease
2012Co-Authors: María G. Álvarez, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Rodolfo ViottiAbstract:In 12–18% of adult patients, treatment with Benznidazole for chronic Chagas disease has to be discontinued because of side-effects. We identified and analysed a cohort of 81 adult patients with three positive tests for Trypanosoma cruzi infection and serological monitoring following incomplete treatment with Benznidazole for a median of 10 days. Twenty percent of these patients (16/81) met the criteria of cure, showing that the optimal schedule of Benznidazole administration remains to be determined.
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side effects of Benznidazole as treatment in chronic chagas disease fears and realities
2009Co-Authors: Rodolfo Viotti, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Maria Gabriela Alvarez, Alejandro ArmentiAbstract:Chagas disease is caused by a parasite, Trypanosoma cruzi, transmitted primarily by a triatomine insect and affects approximately 8 million people in Latin American countries. The principal aim of the management of the disease is to avoid the development of cardiomyopathy and transmission by blood transfusion, congenital and organ transplants. Currently, Benznidazole is the only etiological treatment commercially available for the disease until new and better drugs can be developed and tested. Benznidazole has been used even though it does not have all the conditions of an ideal drug. The efficacy and tolerance of Benznidazole is inversely related to the age of the patient, while its side effects are more frequent in elderly patients. The side effects are systematically evaluated only in controlled studies designed for that purpose. However, the true clinical impact of the side effects could be different, considering that the treatment is for a short duration (between 30 and 60 days) and only carried out ...
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long term cardiac outcomes of treating chronic chagas disease with Benznidazole versus no treatment
2006Co-Authors: Rodolfo Viotti, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Maria Gabriela Alvarez, Miriam Postan, Alejandro ArmentiAbstract:The authors assigned alternate patients with chronic Chagas disease to treatment with Benznidazole or to no treatment and followed them for a mean of approximately 10 years. The patients had no evi...
Bruno Lococo - One of the best experts on this subject based on the ideXlab platform.
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Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study.
2017Co-Authors: María G. Álvarez, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Rodolfo ViottiAbstract:Abstract Since the decline in new cases of infection by insect/vector, congenital Chagas disease has become more relevant in the transmission of Chagas disease. Treatment with Benznidazole significantly reduces the parasitemia, which constitutes an important factor linked to vertical transmission. The objective of this study was to evaluate whether treatment with Benznidazole previously administered to women of childbearing age can prevent or reduce the incidence of new cases of congenital Chagas disease. An historical cohort study that included all women in reproductive age (15–45 years) assisted in our center was designed. We included 67 mothers with chronic Chagas disease; 35 women had not been treated prior to pregnancy, 15 had been treated prior to pregnancy and 17 gave birth prior and after treatment with Benznidazole. Eight mothers gave birth to 16 children with congenital Chagas disease (8/67, 12%). The prevalence of congenital Chagas was 16/114 (14%) children born to untreated mothers and 0/42 (0%) children born to Benznidazole- treated mothers, p = 0.01. No significant differences were observed in clinical, serologic, epidemiological or socioeconomic baseline variables between mothers with and without children born with congenital Chagas. A 32% conversion rate to negative serology was observed in Benznidazole-treated women after long-term follow up. Antiparasitic treatment administered to women in reproductive age can prevent the occurrence of congenital Chagas disease.
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new scheme of intermittent Benznidazole administration in patients chronically infected with trypanosoma cruzi a pilot short term follow up study with adult patients
2016Co-Authors: Maria Gabriela Alvarez, Bruno Lococo, Graciela Bertocchi, Alejandro G Schijman, Yolanda Hernandez, Marisa M Fernandez, Juan Carlos Ramirez, Carolina Cura, Constanza Lopez Albizu, Marcelo AbrilAbstract:There is a clinical need to test new schemes of Benznidazole administration that are expected to be at least as effective as the current therapeutic scheme but safer. This study assessed a new scheme of Benznidazole administration in chronic Chagas disease patients. A pilot study with intermittent doses of Benznidazole at 5 mg/kg/day in two daily doses every 5 days for a total of 60 days was designed. The main criterion of response was the comparison of quantitative PCR (qPCR) findings prior to and 1 week after the end of treatment. The safety profile was assessed by the rate of suspensions and severity of adverse effects. Twenty patients were analyzed for safety, while qPCR was tested for 17 of them. The average age was 43 ± 7.9 years; 55% were female. Sixty-five percent of treated subjects showed detectable qPCR results prior to treatment of 1.45 (0.63 to 2.81) and 2.1 (1.18 to 2.78) parasitic equivalents per milliliter of blood (par.eq/ml) for kinetoplastic DNA (kDNA) qPCR and nuclear repetitive sequence satellite DNA (SatDNA) qPCR, respectively. One patient showed detectable PCR at the end of treatment (1/17), corresponding to 6% treatment failure, compared with 11/17 (65%) patients pretreatment (P = 0.01). Adverse effects were present in 10/20 (50%) patients, but in only one case was treatment suspended. Eight patients showed mild adverse effects, whereas moderate reactions with increased liver enzymes were observed in two patients. The main accomplishment of this pilot study is the promising low rate of treatment suspension. Intermittent administration of Benznidazole emerges a new potential therapeutic scheme, the efficacy of which should be confirmed by long-term assessment posttreatment.
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seronegative conversion after incomplete Benznidazole treatment in chronic chagas disease
2012Co-Authors: María G. Álvarez, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Rodolfo ViottiAbstract:In 12–18% of adult patients, treatment with Benznidazole for chronic Chagas disease has to be discontinued because of side-effects. We identified and analysed a cohort of 81 adult patients with three positive tests for Trypanosoma cruzi infection and serological monitoring following incomplete treatment with Benznidazole for a median of 10 days. Twenty percent of these patients (16/81) met the criteria of cure, showing that the optimal schedule of Benznidazole administration remains to be determined.
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side effects of Benznidazole as treatment in chronic chagas disease fears and realities
2009Co-Authors: Rodolfo Viotti, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Maria Gabriela Alvarez, Alejandro ArmentiAbstract:Chagas disease is caused by a parasite, Trypanosoma cruzi, transmitted primarily by a triatomine insect and affects approximately 8 million people in Latin American countries. The principal aim of the management of the disease is to avoid the development of cardiomyopathy and transmission by blood transfusion, congenital and organ transplants. Currently, Benznidazole is the only etiological treatment commercially available for the disease until new and better drugs can be developed and tested. Benznidazole has been used even though it does not have all the conditions of an ideal drug. The efficacy and tolerance of Benznidazole is inversely related to the age of the patient, while its side effects are more frequent in elderly patients. The side effects are systematically evaluated only in controlled studies designed for that purpose. However, the true clinical impact of the side effects could be different, considering that the treatment is for a short duration (between 30 and 60 days) and only carried out ...
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long term cardiac outcomes of treating chronic chagas disease with Benznidazole versus no treatment
2006Co-Authors: Rodolfo Viotti, Carlos Vigliano, Bruno Lococo, Graciela Bertocchi, Marcos Petti, Maria Gabriela Alvarez, Miriam Postan, Alejandro ArmentiAbstract:The authors assigned alternate patients with chronic Chagas disease to treatment with Benznidazole or to no treatment and followed them for a mean of approximately 10 years. The patients had no evi...