Efectos adversos del benznidazol en el tratamiento de la enfermedad de Chagas

Abstract

Objectives: A1. To describe, by retrospective assessment, benznidazole’s adverse effects in Chagas chronic disease’ diagnosed adults. A2. To test if our cohort results match with previously described by smaller cohorts. A3. To evaluate the severity of these effects and the rate of withdrawals related. A4. To prospectively analyse benznidazole’s adverse effects in a subcohort of Chagas chronic disease’ adults recently diagnosed. B1. To describe benznidazole’s adverse effects in pregnant women who took this medication during their pregnancy. B2. To carry on a temporary follow-up of these newborns in order to know the posible consequences of the treatment on their state of health. C1. To assess whether there is a statistically significant relationship between being a carrier of a certain HLA-B (HLA-B*35 or specifically HLA-B*35:05) and the development of benznidazole’s adverse effects. C2. To study if performing a patch test is effective as a predictor of a potential skin disorder benznidazole related. Methodology: Three studies about benznidazol’s adverse effects related to Chagas disease, were carried out in this investigation. The first study was a retrospective collection of data from pregnant women treated with benznidazole, their newborns, and a subsequent follow-up. The second study was divided into two subcohorts, a retrospective one focused on adverse effects in adults treated with the drug, and another prospective one collecting adverse reaction data through telephone calls. Finally, a retrospective study was carried out analyzing the relationship between the HLA-B*35 gene and a patch test with adverse effects in adults treated with benznidazole. Conclusions: 1. Although in smaller cohorts digestive effets are second in frequency after cutaneous ones, in our retrospective study with more tan 700 patients they were the least frequent (20-30% versus 5%). 2. Being female and suffering from skin disorders were significantly related to benznidazole withdrawal. 3. A significant part of suffered adverse effects are underestimated or forgotten at the post-treatment medical appointment, however, our prospective study reveals that up to 100% of patients suffer from them, being headache the most frequent (39.5%). 4. Apparently, there seems to be no relation between a closer follow-up and the frequency of benznidazol withdrawls, however, while discontinuation of treatment was related to various reasons both medical and non-medical in the retrospective study, withdrawals in the prospective study were exclusively adverse effects. 5. Although benznidazole is not recommended in pregnant women, in our cohort 4 women took it for at least 15 days (range 15-60) due to ignorance of their status, and no adverse effects or pregnancy problems were detected. 6. Even though not being able to draw conclusions from 4 cases of treated pregnant women, it is encouraging that, despite taking benznidazole in the first trimester, none of the newborns developed any type of malformation. 7. The HLA-B*35 allelic group and specifically HLA-B*35:05 allele is Bolivia’s most frequent HLA-B, and this is confirmed in our patients, not being a statistically significant relationship between adverse effects or withdrawal and this marker. 8. Patch test is rejected as preemptive test for skin disorders due to its low sensitivity.