Chagas disease - Emerging treatments

Drug development for Chagas disease

Drugs that are more effective than benznidazole or nifurtimox are not likely to be available in the near future. However, trials investigating adapted dose regimens for benznidazole are underway, in order to improve compliance and decrease adverse effects while maintaining efficacy. Pharmacokinetic studies of trypanocidal drugs used in clinical practice play a vital role in comprehending the factors associated with adverse events.[198] Research on new drugs and optimized treatment regimens (including combination therapies) are lacking and should be a priority in future trials.[170][199][200] Recent studies show that translational research in Chagas disease, addressing drug combinations and repositioning, is an alternative in improving intolerance to benznidazole and/or nifurtimox, as well as increasing the effectiveness of these drugs.[201] The Drugs for Neglected Diseases Initiative (DNDi) is a nonprofit organization that develops new treatments for Chagas disease, as well as other global infectious diseases. DNDi: Chagas Opens in new window

Fexinidazole

One phase 2 clinical trial assessed the efficacy and safety of fexinidazole, an antiprotozoal agent targeting Trypanosoma cruzi, in patients with indeterminate chronic Chagas disease. The findings highlight the necessity for further research to determine the optimal dose of fexinidazole and its risk-benefit ratio. The results indicate promising potential for treatment regimens lasting less than 10 days.[202]

Isosorbide dinitrate and nifedipine

Isosorbide dinitrate and nifedipine are effective in reducing esophageal symptoms. Isosorbide dinitrate appears to be more effective, and its use is supported by a larger number of studies; however, nifedipine appears to have a better tolerability profile.[203]

Amiodarone

Amiodarone has been widely used for the treatment of arrhythmias in Chagas disease but data are lacking to support its use in Chagas disease specifically. A systematic review found that amiodarone is effective in reducing the incidence of ventricular arrhythmias in patients with Chagas disease; however, there is no evidence for an improvement in clinically relevant outcomes such as hospitality and mortality.[204] Amiodarone is being tested in a phase III trial to see whether treatment for at least 6 months has a trypanocidal effect in patients with mild-to-moderate chronic Chagas cardiomyopathy, and whether there are any clinical benefits from this treatment.[205]

Biomarkers

Studies are ongoing to identify biomarkers which can be used to assess therapeutic accuracy and help to determine which patients are at risk of progression to chronic disease. Various biomarker types have been investigated but none have demonstrated effectiveness in assessing the therapeutic response to trypanocidal treatment.[206]

Stem cell therapy

Cell transplantation with bone marrow stem cells has been suggested as an alternative for heart transplantation in patients with chronic Chagasic cardiomyopathy.[207][208][209][210] The aim of this therapy is not to kill the parasite, but to improve chronic heart disease.[211] In fact, in mice with chronic Chagas infections, bone marrow mononuclear cells from normal donors reduced cardiac inflammation and fibrosis, and prevented right ventricular dilation.[212][213] There is limited evidence demonstrating slight improvement 6 months after autologous bone marrow cell transplantation,[214] although other studies show no such benefit.[215]

Vaccination

For decades, there have been many attempts to develop a Chagas vaccine, but in general, results have not been very promising. Development of an effective vaccine in the near future is not likely.[216][217] There are, however, several candidate proteins of T. cruzithat have been considered for vaccine development (e.g., cruzipain, trans-sialidase, amastigote surface protein).[217][218][219][220][221] Studies have identified more than 30 gene fragments that may be future targets for immunization.[222][223][224][225]