Increased levels of chemokines and cytokines mediators of eosinophil and T cell recruitment in subjects with chronic Chagas disease with hypersensitivity reactions to benznidazole

AILEN NATALE; CASTRO EIRO MELISA; DÉBORA SEIGELFISCHER ; MARIA BELEN CAPUTO; MARISA FERNANDEZ; MARIA J ELIAS; VIOTTI RODOLFO; LOCOCO BE; MARIA CECILIA ALBAREDA; CÉSAR, GONZALO; ALVAREZ MARIA GABRIELA; LAUCELLA, SUSANA A

Maryland

Congreso; ASTMH 70 annual meeting; 2021

Chagas disease is caused by the intracellular parasite Trypanosoma cruzi and it is the main cause of infectious myocardiopathy in the world. Benznidazole and nifurtimox are the two drugs approved for the treatment of Chagas disease. A suspension rate of approximately 17-30 percent primarily due to the appearance of severe dermatitis is observed during treatment with benznidazole in chronic Chagas disease. In this study, 49 adult subjects with diagnosis of T. cruzi infection were recruited prescribed for etiological treatment. The treatment consisted of benznidazole administered at 5 mg/kg body weight per day for 30 days. All subjects with severe dermatitis discontinued benznidazole therapy. Through cytometric bead assays and ELISA capture techniques, we measured the levels of pro-inflammatory cytokines, pro-apoptotic molecules and mediators of activation, differentiation and migration of eosinophils and T cells in the sera of T. cruzi-infected subjects treated with benznidazole who exhibited skin adverse events (n = 23) and compared with those without adverse events (n = 26). The amounts of IL-5, soluble FAS-L, IP-10 and MIG significantly increased at 7-30 days post-treatment and decreased thereafter, in subjects with dermatitis but not in subjects without dermatitis, compared with uninfected subjects. Additionally, granzyme B levels increased in a proportion of the treated subjects who had skin adverse events. In contrast, normal levels of eotaxin were observed in treated subjects with or without dermatitis. The levels of different hematologic parameters, cholesterol and IgE were not found to be predictors of adverse drug reaction. These results support a delayed type hypersensitivity reaction to drugs, with eosinophils and T cell recruitment and release of cytotoxic molecules.