The treatment of Chagas disease patients with nitroderivative is unsatisfactory

Abstract

Re: "Persistent infections in chronic Chagas' disease patients treated with anti-Trypanosoma cruzi nitroderivatives" "Then I would still have this consolation -my joy in unrelenting pain -that I had not denied the words" … Brasília, March 3, 2001Sir,We are honoured to respond to the "Letter to the Editor", which was signed and forwarded for publication in the current issue of this journal by J. Romeu Cançado. First of all, we would like to praise him for the keen interest to open this important subject for discussion, thus recognizing that the treatment of Chagas disease patients with nitroderivatives is as yet unresolved for many physicians assisting people with this life threatening infectious disease, and for us. With respect to this, we appreciate Cançado's acknowledgment of the merit of our article recently published in this journal 6 , whereas we fully reject his comment that "the results shown do not support the conclusion drawn". On the other hand, we clearly understand Cançado's awareness that there is "controversy concerning the etiological treatment of chronic Chagas Disease, chiefly because there is no consensus for the criterion of cure". This controversy may be explained by lack of randomisation of research protocols, and by different criteria in obtaining data published by several authors in the last three decades. We believe that nitroderivatives may be life saving in those few patients with severe clinical manifestation of acute T. cruzi infection, or in immunosuppressed patients undergoing reactivation of the infection, only. We do not indicate treatment of the chronic T. cruzi infections, because we have not found a single benefit resulting from treatment of these Chagas patients with anti-trypanosoma drugs. In conjunction, it holds true that chemotherapy of T. cruzi infections with either benznidazole or nifurtimox nitroderivative is unsatisfactory and cannot be recommended since it fails to eradicate the parasite or to change the progression of heart disease in Chagas patients. Nitroderivatives used for treatment of Chagas Disease:The nifurtimox [4-(5-nitro-phurylideneamino-) tetrahydro-4-4-1, 4-thiazine-1-1-dioxide], and benznidazole [N-benzyl-2-nitro-imidazoleacetamide) are anti-trypanosoma nitroderivatives used to treat T. cruzi infections. Severe cytotoxicity has been described for several nitroderivatives, and, in recent decades, these compounds have been shown to possess a variable degree of mutagenic, teratogenic, carcinogenic and sterilizing activities 4,5,16,17,27,30,37,44,45,47 . Cytotoxicity and genotoxicity associated with nitroderivatives seem to depend on the binding of electrophilic radicals to macromolecules and DNA, after enzymatic reduction of the nitro-group and generation of free electrophilic radicals, such as nitro-anions, hydroxyl, singlet oxygen and hydrogen peroxide 18,21,30,31,41 . The drug toxicity targets the parasite and the mammalian host cell 18,27 . Table 1 shows data from nine research groups of treated acute or recent T. cruzi infections in different regions...