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

Nearly 90 million people (about a quarter of the Latin American population) live in zones where Chagas disease is endemic while 18-20 million are already infected with is causative agent, Trypanosoma (Schizotrypanum) cruzi. It is estimated that there are currently >550,000 new cases and 50,000 deaths associated to this condition every year (Docampo & Schmuñis 1997). This disease leads to an annual loss of 2.7 millions of disability adjusted years, being the largest parasitic disease burden in the continent and only third on a global scale after malaria and schistosomiasis (World Bank 1993). Chemotherapy of this disease is still very unsatisfactory, being based in nitrofurans (nifurtimox, Bayer; recently discontinued) and nitroimidazoles (benznidazole, Roche) developed empirically three decades ago. These compounds have activity in the acute and short-term (up to a few years) chronic phase (Andrade et al.1996), but is efficacy varies according to the geographical area, probably due to differences in drug susceptibility of different T. cruzi strains (Filardi & Brener 1987); however, they have little or no activity in prevalent, long term chronic form of the disease, which is widely considered an incurable disease (Rassi & Luquetti 1992, de Castro 1993, Quintas et al.1996, Andrade et al.1996, Croft et al.1997). Furthermore, both drugs have frequent side effects (generally less severe in pediatric patients) including anorexia, vomiting, peripheral neuropathy and allergic dermopathy (Rassi & Luquetti 1992, de Castro 1993, Quintas et al.1996, Croft et al.1997). Although great advances have been made in recent years in the control of the vectorial and transfusional transmission of the disease, particularly through the Southern Cone Initiative involving Brazil, Argentina, Paraguay and Uruguay, progress is uneven in other parts of the continent and the problem of the persons already infected remains unsolved. In this brief review I would like to discuss recent work, involving the joint effort of biochemists, chemists, parasitologists, molecular and cell biologists and immunologists, that have raised the possibility of radical parasitological cure in chronically infected experimental animals and humans thorough rational chemotherapeutic approaches. I would also like to discuss the role of parasites in the pathogenesis of chronic Chagas disease and thus the relevance of parasitological cure in the clinical outcome of this disease. A more extended version of this discussion has been presented elsewhere (Urbina 1999).