Parasitological cure of Chagas disease: is it possible? Is it relevant?

Abstract

Nearly 90 million people (about a quarter ofthe Latin American population) live in zones whereChagas disease is endemic while 18-20 million arealready infected with is causative agent, Trypano-soma (Schizotrypanum) cruzi. It is estimated thatthere are currently >550,000 new cases and 50,000deaths associated to this condition every year(Docampo & Schmunis 1997). This disease leadsto an annual loss of 2.7 millions of disability ad-justed years, being the largest parasitic diseaseburden in the continent and only third on a globalscale after malaria and schistosomiasis (WorldBank 1993). Chemotherapy of this disease is stillvery unsatisfactory, being based in nitrofurans(nifurtimox, Bayer; recently discontinued) andnitroimidazoles (benznidazole, Roche) developedempirically three decades ago. These compoundshave activity in the acute and short-term (up to afew years) chronic phase (Andrade et al.1996), butis efficacy varies according to the geographicalarea, probably due to differences in drug suscepti-bility of different T. cruzi strains (Filardi & Brener1987); however, they have little or no activity inprevalent, long term chronic form of the disease,which is widely considered an incurable disease(Rassi & Luquetti 1992, de Castro 1993, Quintaset al.1996, Andrade et al.1996, Croft et al.1997).Furthermore, both drugs have frequent side effects(generally less severe in pediatric patients) includ-ing anorexia, vomiting, peripheral neuropathy andallergic dermopathy (Rassi & Luquetti 1992, deCastro 1993, Quintas et al.1996, Croft et al.1997).Although great advances have been made in re-cent years in the control of the vectorial and trans-fusional transmission of the disease, particularlythrough the Southern Cone Initiative involvingBrazil, Argentina, Paraguay and Uruguay, progressis uneven in other parts of the continent and theproblem of the persons already infected remainsunsolved.In this brief review I would like to discuss re-cent work, involving the joint effort of biochem-ists, chemists, parasitologists, molecular and cellbiologists and immunologists, that have raised thepossibility of radical parasitological cure in chroni-cally infected experimental animals and humansthorough rational chemotherapeutic approaches. Iwould also like to discuss the role of parasites inthe pathogenesis of chronic Chagas disease andthus the relevance of parasitological cure in theclinical outcome of this disease. A more extendedversion of this discussion has been presented else-where (Urbina 1999).