allopurinol and Chagas-Cardiomyopathy

Several drugs are now known to have useful activity against Trypanosoma cruzi, the causative agent of human American trypanosomiasis (Chagas disease). However, the long-term effects of chemotherapy on the electrocardiographic (ECG) abnormalities associated with this disease have only been assessed for benznidiazole. In the present study, the ECG changes in 299 cases of chronic Chagas disease were followed for 9 years after treatment with itraconazole (N = 136) or allopurinol (N = 163). Among the 97 cases who were found to have ECG abnormalities immediately prior to their treatment, the two drugs appeared equally effective, such abnormalities being corrected in 23 (50%) of the 46 cardiopathy cases given itraconazole and 25 (49%) of the 51 given allopurinol (P > 0.05). Both of these 'cure rates' are much higher than the 8.1% frequency of abnormal-normal conversion observed among 198 'historical controls' (i.e. cases of chronic Chagas disease who had been left untreated; P < 0.05). Itraconazole appeared better than allopurinol at preventing the development of cardiopathy in the cases who appeared electrocardiographically normal at baseline. Among 202 such cases, only two (2.2%) of the 90 treated with itraconazole but 28 (25.0%) of the 112 given allopurinol were found to have developed ECG abnormalities during follow-up (P < 0.05). Therefore, although itraconazole and allopurinol are equally effective at reversing ECG alterations, itraconazole offers better protection against the development of new ECG abnormalities among those with chronic Chagas disease.

Topics: Adolescent; Adult; Allopurinol; Antiprotozoal Agents; Arrhythmias, Cardiac; Chagas Cardiomyopathy; Chagas Disease; Child; Double-Blind Method; Electrocardiography; Female; Heart Block; Humans; Itraconazole; Male; Middle Aged; Patient Compliance

Four hundred four patients with chronic Chagas' disease were treated with itraconazole (6 mg/kg of body weight/day for 120 days), allopurinol (8.5 mg/kg of body weight/day for 60 days), or with a placebo of pure starch. Patients were monitored over a period of four years by clinical examination, serology, xenodiagnosis, hemoculture, and electrocardiogram. Drug tolerance was good, with only four treatments discontinued due to side effects that subsided after suspension of treatment. Parasitologic cure was evident in 44% of the those treated with allopurinol and 53% of those treated with itraconazole, and the electrocardiographic evaluation showed normalization in 36.5% and 48.2%, respectively, of patients with chronic or recent cardiopathy.

Topics: Adolescent; Adult; Allopurinol; Animals; Antibodies, Protozoan; Antifungal Agents; Antimetabolites; Biological Assay; Chagas Cardiomyopathy; Chagas Disease; Child; Chronic Disease; Double-Blind Method; Electrocardiography; Follow-Up Studies; Humans; Insect Vectors; Itraconazole; Middle Aged; Nymph; Triatoma; Trypanosoma cruzi

Topics: Allopurinol; Chagas Cardiomyopathy; Chagas Disease; Chronic Disease; Clinical Trials as Topic; Female; Humans; Male; Nifurtimox; Nitroimidazoles; Trypanocidal Agents

Topics: Allopurinol; Antimetabolites; Chagas Cardiomyopathy; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Echocardiography; Electrocardiography; Follow-Up Studies; Humans; Nitroimidazoles; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Trypanocidal Agents

In this study is presented the comparative therapeutical experience comparing the Allopurinol, Benznidazol y Nifurtimox, in a prospective following in a long term, considering the responses to the parasitemia, specific serology and evolution of the clinic manifestations and complementaries in the 535 chronic chagasic cases (44.5%), instead of 668 patients who did not get any treatment (1203 chagasic cases followed for more than 5 years average). This study was done between April 1984 and April 1994 in patients with and without cardiopathy, in the Córdoba Hospital and the Salud Estudiantil Direccion, Universidad Nacional de Córdoba (U.N.C.); from them, 309 patients were given Allopurinol, 130 were given Benznidazol, and 96 were given Nifurtimox, with usual doses of Benznidazol and Nifurtimox, but with Allopurinol it was made an study evaluating the answering-doses, with a following time of post-therapeutic average of 55.6 months (D.S. = + -57 m.) The comparative parameters were the starting clinic characteristics, the qualitative and quantitative for Chagas, the pre-treatment xerodiagnostic, the treatment fulfillment, the treatment duration, the adverse effects, the treatment abandon, the time of postreatment longitudinal following till the last clinic-complementary evaluation, the clinic characteristics at the end of the following period; quantitative and qualitative serology for Chagas after the treatment, and post-treatment xerodiagnostic. It was observe a prevalence of Electrocardiographic Changes in the ECG in rest, in the first complementary evaluation in 76 of the 535 "Treated" and in the 225 "No-treated" patients, being Electrocardiographic abnormality proportion much more in the "No-treated" patients (P = 0.000000). After the end of the following period it was thought to have been found Miocardic Damage Progression in 120 patients "No-treated" and in 31 "Treated" patients (17.9% and 5.8% respectively) (P = 0.0000000). The complications in the evolution course were proved in 113 of the "No-treated" and in 19 of the "Treated" patients (16.9% and 3.5%, being this a statistically significant difference (P = 0.0000000). The mortality along the evolution was proved in 37 of the "No-Treated:" patients and in 7 of the "Treated" patients (5.5% and 1.3%), being this a statistically significant difference (P = 0.00019). The most tolerated drug and the one with the least incidence of therapeutic abandons was the Allopurinol. The xerodiagnostic negativization

Topics: Adolescent; Adult; Aged; Allopurinol; Antiprotozoal Agents; Chagas Cardiomyopathy; Chagas Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nifurtimox; Nitroimidazoles; Prospective Studies; Retrospective Studies; Time Factors; Treatment Outcome; Trypanocidal Agents

We describe two patients who underwent cardiac transplantation for chronic cardiomyopathy of Chagas' disease, and in whom the disease was reactivated with the development of cutaneous lesions. In both cases, the skin lesions regressed completely after 2 months of therapy with allopurinol.

Topics: Adult; Allopurinol; Antiparasitic Agents; Chagas Cardiomyopathy; Chagas Disease; Female; Heart Transplantation; Humans; Male; Middle Aged; Recurrence; Skin Diseases, Parasitic; Trypanocidal Agents

Chagas' disease is a parasitic infection that provokes a severe form of dilated cardiomyopathy. In the initial experience with heart transplantation with Chagas' disease, a high rate of acute reactivation has been reported. Although benzinidazole and nifurtimox are effective in the treatment of reactivation or of the acute phase of the disease they are associated with important adverse effects. Allopurinol has substantial activity against Trypanosoma cruzi in vitro, in the experimental laboratory and in chronic human Chagas' disease; however, there is no information regarding its action in Chagas' reactivation after heart transplantation.. We describe two patients with Chagas' disease who underwent heart transplantation. The first one had asthenia, anorexia, and several painful subcutaneous nodules in the legs after transplantation; biopsy showed an inflammatory infiltrate with intracytoplasmatic nests of Trypanosoma cruzi, confirmed by immunohistochemical stains with monoclonal antibodies specific to parasitic antigens. Allopurinol (600 mg/day) produced complete regression of the symptoms and the nodules with a negative control biopsy within 2 weeks. Treatment was maintained for 2 months. Mild leukopenia developed which improved after azathioprine reduction, and no further side-effects were noted. The second patient had sudden heart failure months after transplantation; endomyocardial biopsy showed myocardial fibers infested with Trypanosoma, and a concomitantly performed right heart catheterization showed a low cardiac index and highfilling pressures. The patient received allopurinol at a daily dose of 900 mg and conventional treatment for heart failure. Echocardiogram showed improved wall motion and decreased left ventricular dimensions, and control biopsy showed no inflammatory activity; cardiac index and filling pressures normalized. Treatment was maintained for 2 months without side effects. The two patients have not had recurrences and were in New York Heart Association functional class I 12 and 3 months, respectively, after discontinuation of allopurinol.. Allopurinol seems to be safe and effective in treating Chagas' disease reactivation after heart transplantation. A larger number of case studies seems to be necessary to properly evaluate its role in the treatment of Chagas' disease reactivation.

Topics: Adult; Allopurinol; Chagas Cardiomyopathy; Chagas Disease; Heart Failure; Humans; Immunosuppression Therapy; Male; Middle Aged; Recurrence