Tratamento da forma indeterminada da doença de Chagas com nifurtimox e benzonidazol

Abstract

One hundred patients with the indeterminate form of human chronic Chagas disease were submitted to chemotherapy, 50 with nifurtimox (Bayer) and 50 with benznidazole (Roche) from 1965 up to 1985. After two-year follow-up there was negativation of xenodiagnosis in 25 (50%) and negativation of serological tests in 3 (6%) of the patients treated with nifurtimox. As for benznidazole there was 35 (70%) of xenodiagnosis negativation and 5 (10%) of serological negativation. In 92 patients after a period of 24 month follow-up there was at least one kind of positive test, indicating therapeutic failure. Eight patients with negative xenodiagnosis and serological tests were considered cured. The average follow-up in patients treated with nifurtimox and benznidazole were respectively 17.3 and 7 years.

The treatment of Chagas disease patients with nitroderivative is unsatisfactory

“…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. SILVEIRA 38 and SILVEIRA et al 39 reported 17.2% of cure after nitroderivative therapy of chronic Chagas patients showing decreasing titers of specific antibodies in three different serologic tests.…”

“…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 .…”

Chagas' heart disease

“…Evidence for potential benefits of specific antitrypanosoma chemotherapy in chronic Chagas' heart disease is lacking because misleading criteria have been used to assess therapeutic efficacy and also due to the fact that only small, nonrandomized, noncontrolled trials have been carried out [169][170][171] . Thus, conversion from a serum-positive to a serum-negative state following therapy is an unreliable marker of the impact of such treatment upon the course of Chagas' disease, because in any event, negative serology is common in the chronic phase.…”

“…Hence, results of any of the serological criteria used to assess the therapeutic value of etiologic treatment in patients with the chronic form of Chagas' heart disease are clearly unreliable. The reported rate of negativity of serological tests following treatment in the chronic phase is consistently very low (4-8%) in the trials suffering the epidemiological restrictions already pointed out [169][170][171] . Thus, until an adequate laboratory method is available for assessment of cure, the only acceptable criteria for any etiologic therapeutic intervention benefit must be based on the prevention of the appearance of the clinical form of disease or the arrest of progression of the damage already detected.…”

Progressive chronic Chagas heart disease ten years after treatment with anti-Trypanosoma cruzi nitroderivatives.

“…[5][6][7] Nevertheless, nitroderivative compounds with anti-trypanosomal activity have been used to treat T. cruzi infections in humans. [8][9][10][11][12][13][14] Benznidazole (N-benzyl-2-nitro-imidazoleacetamide) and nifurtimox (4-[5-nitro-3-methyl-furphurylideneamino]-tetrahydro-4-H-1, 4-thiazine-1-1-dioxide) curtail parasitemias and are indicated for treating acute Chagas disease. [9][10][11] However, these drugs cannot be administered without the supervision of a physician because they provoke undesirable side effects.…”