Itraconazole or allopurinol in the treatment of chronic American trypanosomiasis: the results of clinical and parasitological examinations 11 years post-treatment

Abstract

Eleven years after they had been given itraconazole or allopurinol for the treatment of chronic American trypanosomiasis, 109 adult patients were checked for electrocardiographic abnormalities and evidence of Trypanosoma cruzi infection. The parasitological investigations included xenodiagnosis, in which the faeces of Triatoma infestans that had fed on the patients were checked under the microscope for flagellates. In addition, a PCR-based assay and a hybridization assay were used to test blood samples from the patients, and faeces from the Tri. infestans that had fed on the patients, for Try. cruzi DNA. For the data analysis, the patients were divided into four groups known as normal/normal, abnormal/normal, normal/abnormal and abnormal/abnormal, according to whether the patients had been found to have normal or abnormal electrocardiograms (ECG) shortly before the first treatment and to have normal or abnormal ECG when checked at the 11-year follow-up. The 51 normal/normal and 24 normal/abnormal patients were assumed to have been in the 'indeterminate' phase of the disease when they were treated, whereas the 16 abnormal/normal and 18 abnormal/abnormal patients all had evidence of chagasic cardiopathy at that time. When checked 11 years post-treatment, 40 (78.4%), 17 (70.8%), 14 (87.5%) and 17 (94.4%) of these patients, respectively, were each found positive for Try. cruzi in at least one of the parasitological tests. The hybridization assay, whether applied to human blood or bug faeces, appeared a significantly more sensitive test than the PCR-based assays or microscopically assessed xenodiagnosis (P<0.05). Only the 21 patients who appeared to be negative for Try. cruzi could be considered parasitologically cured (although all still appeared to have anti-Try. cruzi antibodies in their blood). Only 13 of these parasitologically cured patients (seven of those treated with itraconazole and six of those given allopurinol) had normal ECG at the 11-year follow-up. In Chile at least, itraconazole, which caused fewer adverse effects than the allopurinol while being no less effective at preventing cardiopathy, appears to be the drug of choice to treat chronic American trypanosomiasis in adults.

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

“…Numerous natural and synthetic chemical compounds with potential trypanocidal activity are being added to the list, including allopurinol and its analogues, ketoconazole and itraconazole (antifungal imidazoles), quinones, diverse nitroheterocyclic derivatives, antioxidants and other drugs in clinical use, such as phenothiazines (Apt et al, 2005;Maya et al, 2007;Urbina, 2009b). Some compounds, including sterol biosynthesis, cysteine protease and pyrophosphate metabolism inhibitors, have completed pre-clinical studies and are poised for clinical trials in Chagas disease patients (Reithinger et al, 2009;Urbina, 2009a).…”

Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies

“…However, due to their well-known toxicity and limited effect towards different parasite isolates and disease phases (primarily patients in the later chronic phase), new drugs are urgently needed (Coura & De Castro 2002, Soeiro & De Castro 2009. While many trypanocidal compounds have been screened in the past few decades and some promising targets have been reported since the introduction of Nf andBz (1960-1970), only allopurinol and a limited number of azoles, such as itraconazole, fluconazole and ketoconazole have moved to clinical trials (Brener et al 1993, Solari et al 1993, Apt et al 2005. This situation may reflect (i) low investments in this area, primarily by the pharmaceutical industry, (ii) the misconception that during the later stages of the disease the parasite is absent and thus does not correlate with disease outcome and pathogenesis, and (iii) the lack of standardised protocols for drug screening.…”

Mannose-Binding Lectin and Toll-Like Receptor Polymorphisms and Chagas Disease in Chile

“…9 In this area, a cohort of patients has been regularly followed-up since the 1990s. 10 In these patients and healthy individuals, we typed common SNPs that reduce the function of TLRs involved in the recognition of T. cruzi as well as low-producer MBL2 alleles and analyzed associations with CD and CCC.…”