Current trends in the pharmacological management of Chagas disease

Abstract

Chagas disease (CD) is a tropical neglected illness, affecting mainly populations of low socioeconomic status in Latin America. An estimated 6 to 8 million people worldwide are infected with Trypanosoma cruzi, the etiological agent of CD. Despite being one of the main global health problems, this disease continues without effective treatment during the chronic phase of the infection. The limitation of therapeutic strategies has been one of the biggest challenges on the fight against CD. Nifurtimox and benznidazole, developed in the 1970s, are still the only commercial options with established efficacy on CD. However, the efficacy of these drugs have a proven efficacy only during early infection and the benefits in the chronic phase are questionable. Consequently, there is a growing need for new pharmacological alternatives, either by optimization of existing drugs or by the formulation of new compounds. In the present study, a literature review of the currently adopted therapy, its concomitant combination with other drugs, and potential future treatments for CD was performed, considering articles published from 2012. The revised articles were selected according to the protocol of treatment: evaluation of drug association, drug repositioning and research of new drugs. As a result of the present revision, it was possible to conclude that the use of benznidazole in combination with other compounds showed better results when compared with its use as a single therapy. The search of new drugs has been the strategy most used in pursuing more effective forms of treatment for CD. However, studies have still focused on basic research, that is, they are still in a pre-clinical stage, using methodologies based on in vitro or in animal studies.

Experimental Nanovaccine Offers Protection Against Repeat Exposures to Trypanosoma cruzi Through Activation of Polyfunctional T Cell Response

“…Further, T. cruzi isolates from heterogenous background are not equally susceptible to these drugs (37,38). It is, thus, believed by the research community that an overall increase in access to antiparasite therapies will limit the disease progression in infected individuals and vaccines are needed to prevent the spread of T. cruzi and Chagas disease (39,40). Historically, pathogenbased attenuated vaccines (e.g., smallpox, plague, and measles) are shown to elicit robust immunity and provide protection from repeat infections (41)(42)(43)(44).…”

The Drugs of Sleeping Sickness: Their Mechanisms of Action and Resistance, and a Brief History

“…Nifurtimox (22) has been used since 1969 against Trypanosoma cruzi (i.e., Chagas Disease) [160,161] and, given the urgent need to replace melarsoprol for late-stage HAT, has been investigated as a possible treatment for African trypanosomiasis as well [69]. As related by Janssens and De Muynck [162], the first tests with nifurtimox against African trypanosomiasis were conducted by Marc Wéry who found, apparently to everybody's great surprise, 'a definite activity on the chronic infection' in rats, justifying a first trial in humans.…”

Of Drugs and Trypanosomatids: New Tools and Knowledge to Reduce Bottlenecks in Drug Discovery

“…The cost of Chagas disease was estimated in 2013 at more than US$ 7 B/year, including lost productivity [ 7 ]. However, and despite these alarming numbers, only two toxic, old-fashioned compounds, benznidazole and nifurtimox ( Figure 1 ), are approved for the treatment of Chagas disease [ 6 , 8 ]. While benznidazole is only FDA-approved for pediatric and acute cases of T. cruzi infection, nifurtimox is still only available under compassionate-use directives from the CDC [ 9 , 10 ].…”