Trypanocidal drugs for late stage, symptomatic Chagas disease

Infection with the parasite Trypanosoma cruzi causes American trypanosomiasis or Chagas disease. There is evidence that trypanocidal drug treatment, using nitrofuran and imidazolic compounds, can treat acute trypanosomiasis cruzi infections. However, it is not clear if these interventions are effective for chronic infection specifically overt, chronic Chagasic cardiomyopathy. We systematically reviewed the literature for randomized, double blind, controlled clinical trials with or without placebo published since 1965 when these treatments first became available. We found a single double blind randomized clinical trial and five case-control or case series which addressed trypanocidal treatment of chronic Typanosoma cruzi infection (chronic Chagas disease) in human beings. After reviewing this limited evidence we concluded that treatment with these drugs is not sufficiently well supported regarding clinical value and capacity to eliminate tissue parasitism or induce disappearance of circulating antibodies. Currently new drugs are being developed and clinical trials are needed to evaluate their use in chronic Typanosoma cruzi infection and related diseases.

Authors' conclusions: 

Until now there is insufficient evidence to support the efficacy of nitrofurans or imidazolic drugs as recommended treatment in CCC and chronic T.cruzi infections, specifically if overt heart disease is present. A well designed randomized controlled trial is now ongoing which will clarify the efficacy of these drugs, however, it is necessary to establish if new drugs are suitable for treatment of cardiac patients with CCC.

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Background: 

People with Chagas disease (American Trypanosomiasis) may develop progressive and potentially lethal heart conditions. Drugs to eliminate the causative parasite, Trypanosoma cruzi, currently in use have limited therapeutic value and are used in early stages of the disease. Extending the use of these drugs to treat symptomatic chronic parasitism with chronic Chagasic cardiopathy (CCC) and progressive dilated cardiomyopathy has been proposed.

Objectives: 

To update the systematic review which assessed the effects (harms and benefits) of nitrofurans and imidazolic trypanocidal drugs for treating late stage chronic Chagas disease and CCC.

Search strategy: 

The searches from 2008 were re-run on 31 March 2010 on the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 1, 2010), MEDLINE (OVID) (1985 to March 2010), EMBASE (OVID) (1985 to March 2010) and LILACS (1985 to March 2010). The searches of BIREME (1985-2004), ARTEMISA (1985-2004) and SCIELO (1985-2004) were last run in 2004. Indexing terms in English and Spanish were used. No language restrictions were applied.

Selection criteria: 

We included randomized controlled clinical trials (RCTs), single or double blind using trypanocidal drugs versus placebo or no treatment in CCC.

Data collection and analysis: 

All articles retrieved were assessed by two reviewers independently, using a predefined check list to determine if they met the inclusion criteria. Two independent reviewers collected data using a pre-designed form piloted on three articles before the review process started. Disagreements were resolved by a third reviewer. If the information was unavailable the articles were excluded. We planned a quantitative analysis of reduction of parasite load whether recorded as a categorical variable or the reduction of specific antibody titers. However insufficient data were available for quantitative analysis. We prepared a qualitative description of data identified.

Main results: 

The updated searches did not identify any new trials. One ongoing study has been added for later evaluation. Previously only one randomized double blind placebo controlled trial and five uncontrolled or non-randomized studies which were of some relevance were found.

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