Chronic Chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the BENznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial

Neto, J A Marin; Rassi, Anis

doi:10.1590/0074-02760160334

Cited by 151 publications

(134 citation statements)

References 64 publications

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“…[10] Clinical treatment with Bnz is long, lasting up to 90 days (with doses of 5-7 mg kg −1 day −1 ), and the treatment cures 60%-80% of patients in the acute phase. [11] However, in the chronic phase of the disease, approximately ≥80% of the treated patients are not cured. [12] In addition to being genotoxic, this drug can also cause muscle pain, joint pain, paraesthesia, cutaneous hypersensitivity with the appearance of rash, generalized oedema, thrombocytopenia, fever, lymphadenopathy, purpura and agranulocytosis, peripheral neuropathy and polyneuropathy.…”

Section: Introductionmentioning

confidence: 99%

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

et al. 2018

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Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas' disease.

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Section: Introductionmentioning

confidence: 99%

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

et al. 2018

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“…In the chronic phase, T. cruzi can only be detected from a limited number of patients by parasitological methods, such as xenodiagnosis or blood culture 4,[20][21][22][23] . Therefore, the development of additional molecular methods is necessary for parasite detection in patients with unclear serology and for better evaluation of the roles of specific trypanocidal treatments in patients with established Chagas' cardiomyopathy [24][25][26] . In addition, these tools are important for studies involving biological and genetic characterization of the parasite.…”

Section: Introductionmentioning

confidence: 99%

Combined parasitological and molecular-based diagnostic tools improve the detection of Trypanosoma cruzi in single peripheral blood samples from patients with Chagas disease

Volpato

Sousa

D’Ávila

et al. 2017

Rev. Soc. Bras. Med. Trop.

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Introduction:In order to detect Trypanosoma cruzi and determine the genetic profiles of the parasite during the chronic phase of Chagas disease (ChD), parasitological and molecular diagnostic methods were used to assess the blood of 91 patients without specific prior treatment. Methods: Blood samples were collected from 68 patients with cardiac ChD and 23 patients with an indeterminate form of ChD, followed by evaluation using blood culture and polymerase chain reaction. T. cruzi isolates were genotyped using three different genetic markers. Results: Blood culture was positive in 54.9% of all patients, among which 60.3% had the cardiac form of ChD, and 39.1% the indeterminate form of ChD. There were no significant differences in blood culture positivity among patients with cardiac and indeterminate forms. Additionally, patient age and clinical forms did not influence blood culture results. Polymerase chain reaction (PCR) was positive in 98.9% of patients, although comparisons between blood culture and PCR results showed that the two techniques did not agree. Forty-two T. cruzi stocks were isolated, and TcII was detected in 95.2% of isolates. Additionally, one isolate corresponded to TcIII or TcIV, and another corresponded to TcV or TcVI. Conclusions: Blood culture and PCR were both effective for identifying T. cruzi using a single blood sample, and their association did not improve parasite detection. However, we were not able to establish an association between the clinical form of ChD and the genetic profile of the parasite.

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“…It is estimated that 5% to 8% of the patients with Chagas disease will have megaesophagus 8 . Crema et al 9 carried out 60 esophagectomy surgeries and all patients had advanced megaesophagus, 88.33% secondary to Chagas disease and 11.67% idiopathic cases.…”

Section: ■ Discussionmentioning

confidence: 99%

Combination of preoperative pulmonary and nutritional preparation for esophagectomy

et al. 2018

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Purpose: To compare pulmonary and nutritional parameters before and after inspiratory muscle training (IMT) and enteral feeding support in patients with esophageal disease undergoing preoperative outpatient follow-up. Methods: Thirty patients with a mean age of 55.83 years, 16 men and 14 women, were included. Pulmonary assessment consisted of the measurement of MIP, MEP, and spirometry. Anthropometric measurements and laboratory tests were performed for nutritional assessment. After preoperative evaluation, inspiratory muscle training and enteral nutrition support were started. A p<0.05 was considered statistically significant. Results: After an outpatient follow-up period of 4 weeks, a significant increase in MIP (-62.20 ± 25.78 to -81.53 ± 23.09), MEP (73.4 ± 31.95 to 90.33 ± 28.39), and FVC (94.86 ± 16.77 to 98.56 ± 17.44) was observed. Regarding the anthropometric variables, a significant increase was also observed in BMI (20.18 ± 5.04 to 20.40 ± 4.69), arm circumference (23.38 ± 3.28 to 25.08 ± 4.55), arm muscle circumference (21.48 ± 3.00 to 22.07 ± 3.36), and triceps skinfold thickness (5.62 ± 2.68 to 8.33 ± 6.59). Conclusion: Pulmonary and nutritional preparation can improve respiratory muscle strength, FVC and anthropometric parameters. However, further studies are needed to confirm the effectiveness of this preoperative preparation.

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Chronic Chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the BENznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial

Cited by 151 publications

References 64 publications

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

Combined parasitological and molecular-based diagnostic tools improve the detection of Trypanosoma cruzi in single peripheral blood samples from patients with Chagas disease

Combination of preoperative pulmonary and nutritional preparation for esophagectomy

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