Trypanocidal drugs for late stage, symptomatic Trypanosoma cruzi infection (Chagas disease)

Reyes, Pedro Pa; Vallejo, Maite M

doi:10.1002/14651858.cd004102

Cited by 23 publications

(26 citation statements)

References 13 publications

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“…Systematic reviews of published controlled trials on both asymptomatic individuals and patients with overt Chagas cardiomyopathy, however, showed that there are insufficient data to provide evidence that currently available trypanocidal therapy can alter clinical outcomes in chronic Chagas disease. 149,150 The BENEFIT Trial (Benznidazole Evaluation for Interrupting Trypanosomiasis): Evaluation of the Use of an Antiparasital Drug (Benznidazole) in the Treatment of Chronic Chagas Heart Disease, a large, randomized, doubleblind, controlled study of benznidazole versus placebo in patients with chronic Chagas heart disease, is currently being performed to overcome this therapeutic dilemma.…”

Section: Marin-neto Et Al Pathogenesis Of Chagas Heart Disease 1119mentioning

confidence: 99%

Pathogenesis of Chronic Chagas Heart Disease

Marin-Neto

Cunha-Neto²,

Maciel³

et al. 2007

Circulation

711

640

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Background-Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. Methods and Results-A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Conclusions-Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.

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Section: Marin-neto Et Al Pathogenesis Of Chagas Heart Disease 1119mentioning

confidence: 99%

Pathogenesis of Chronic Chagas Heart Disease

Marin-Neto

Cunha-Neto²,

Maciel³

et al. 2007

Circulation

711

640

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“…This is supported by clinical non-randomized studies, where the use of Bz was associated with reduced progression of Chagas disease and increased negative seroconversion in patients presenting non-acute disease and no heart failure (Marin-Neto et al, 2009;Viotti et al, 2006). Large-scale randomized controlled studies are in progress to provide experimental evidence supporting any recommendation about the clinical use of trypanocide therapy for improving clinical outcomes in chronic and asymptomatic T. cruzi infection (Marin-Neto and Marin-Neto et al, 2008;Reyes and Vallejo, 2005). It is should be noted that there is not curative treatment for chronic Chagas heart disease.…”

Section: Role Of Anti-chagasic Therapy In the Chronic Cardiomiopathymentioning

confidence: 99%

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

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“…In fact, Bz has been used not only in the acute phase, but also in the indeterminate and even in the chronic phase with some positive results, according to several researchers (Viotti et al 1994, Pinto Dias et al 2000, Fabbro et al 2000, García et al 2005, Reyes & Vallejo 2005, Sosa-Estani & Segura 2006. In light of the above described considerations, the potential use of Nfx in the chronic or even in the indeterminate phase of Chagas disease should be considered with caution, since oxidative damage was reported to occur during development of the cardiomyopathy itself (Wen et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The available studies were independently analyzed by Reyes and Vallejo (2005). They concluded that there is still insufficient evidence to support the efficacy of either drug as a recommended treatment for chronic chagasic cardiopathy, if overt heart disease is present.…”

Section: Discussionmentioning

confidence: 99%