Etiological treatment of chronic Chagas disease

Cançado, J. R.

doi:10.1590/s0036-46652001000300012

Cited by 5 publications

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“…Another proof of the presence of the parasite in long standing Chagas disease patients is the finding, by polymerase chain reaction (PCR), of T. cruzi DNA in the peripheral blood of those patients 10 , as we have shown 21 .…”

Section: Discussionmentioning

confidence: 85%

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Long term evaluation of etiological treatment of Chagas disease with benznidazole

Cançado

2002

Rev. Inst. Med. trop. S. Paulo

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272

175

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The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for the chronic patients. The duration of the acute as well as the chronic disease, a condition which influences the results of the treatment, was determined. The therapeutic schedule was presented, with emphasis on the correlation between adverse reactions and the total dose of 18 grams, approximately, as well as taking into consideration precautions to assure the safety of the treatment. Quantitative serological reactions consisting of complement fixation, indirect immunofluorescence, indirect hemagglutination, and, occasionally, ELISA, were used. Cure was found in 76 per cent of the acute patients but only in 8 per cent of those with chronic forms of the disease. In the light of such contrasting results, fundamentals of the etiological therapy of Chagas disease were discussed, like the criterion of cure, the pathogenesis and the role of immunosuppression showing tissue parasitism in long standing chronic disease, in support of the concept that post-therapeutic consistently positive serological reactions mean the presence of the parasite in the patient's tissues. In relation to the life-cycle of T. cruzi in vertebrate host, there are still some obscure and controversial points, though there is no proof of the existence of resistant or latent forms. However, the finding over the last 15 years, that immunosuppression brings about the reappearance of acute disease in long stand chronic patients justifies a revision of the matter. Facts were quoted in favor of the treatment of chronic patients.

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Section: Discussionmentioning

confidence: 85%

“…The data derived from this work, specially on etiological treatment, are included in several academic theses and controlled clinical trials, chapters of books as well as research articles, as cited elsewhere 8,15,16,17,18,19,20,21,37,38,39,49 .…”

Section: Introductionmentioning

confidence: 99%

Long term evaluation of etiological treatment of Chagas disease with benznidazole

Cançado

2002

Rev. Inst. Med. trop. S. Paulo

Self Cite

272

175

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“…There is an even greater divergence of opinion concerning the treatment of cardiopathic patients [19][20][21][22]. Electrocardiographic dysfunctions are irreversible in slighter forms of chagasic cardiopathies.…”

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confidence: 99%

Immunotherapy of Trypanosoma Cruzi Infections

Chamond

Coatnoan²,

Minóprio³

2002

CDTIEMD

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The protozoan parasite Trypanosoma cruzi, causative agent of Chagas' disease, is transmitted to man and other mammals by triatominae insects, or 'kissing bugs'. Since its discovery in 1909, by Carlos Chagas, this parasite has been the object of several publications in the domains of immunology, cellular biology and of control gene organization, regulation and expression. Although much progress has been made concerning prophylaxis of Chagas' disease, particularly vector eradication, additional cases of infection and disease development still occur every day throughout the world. Whilst infection was largely limited in the past to vector transmission in endemic areas of Latin America, its impact has increased in terms of congenital and blood transmission, transplants and recrudescence following immunosuppressive states. Reports on new insect vectors adapted to the parasite and domestic animals infected in more developed countries, emphasize the continuing worldwide public health issue. Therapy against this parasite is limited and cure is subjected to several criteria, such as susceptibility of the parasite strain, age of the host and stage of the disease. The ability of Trypanosoma cruzi to induce important and various host immune system dysfunctions makes the development of effective vaccines a laborious and complex task. These considerations strengthen the latent significance of Chagas' disease and encourage the search for new preventive procedures and the research on rational vaccines.

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“…Of interest, reported data 2,40 showing spontaneous seroconversion, respectively in 5.5% to 4.5% of placebo treated Chagas patients awaits further investigation. These observations need to be considered vis a vis reported success in the nitroderivative treatment of Chagas patients [7][8][9][10][11]19,20 . Furthermore, reported success in treatment of T. cruzi infection should be analysed with further caution, because progression of heart lesions in treated patients has been reported on three different occasions 3,29,36 .…”

Section: Nitroderivatives Used For Treatment Of Chagas Diseasementioning

confidence: 99%

“…In contrast, it seems to us that the data resulting from 11 series of chronic Chagas disease patients shown in Tables 1 and 2 do not support the recommendation by that panel of experts. For example, whereas CANÇADO et al 11 , reported 76% of cure of acute Chagas disease patients treated with nitroderivatives, the ratio of cure of chronic Chagas patients treated with the drug reached 8%, after 6 to 18 years of follow-up [7][8][9][10] . This latter data is in keeping with FERREIRA 20 , who showed 8% of sustained seroconversion in nitroderivative treated chronic Chagas patients in the same time span.…”

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The treatment of Chagas disease patients with nitroderivative is unsatisfactory

2001

Rev. Inst. Med. trop. S. Paulo

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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...

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Etiological treatment of chronic Chagas disease

Cited by 5 publications

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Long term evaluation of etiological treatment of Chagas disease with benznidazole

Long term evaluation of etiological treatment of Chagas disease with benznidazole

Immunotherapy of Trypanosoma Cruzi Infections

The treatment of Chagas disease patients with nitroderivative is unsatisfactory

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