A comparative study of posaconazole and benznidazole in the prevention of heart damage and promotion of trypanocidal immune response in a murine model of Chagas disease.
A comparative study was performed between the trypanocidal efficacy of and associated immune response to benznidazole and posaconazole in a murine model of Chagas disease. Both drugs led to 100% survival, suppression of parasitaemia and reduction of specific anti-Trypanosoma cruzi antibodies following chronic infection. All posaconazole-treated animals had negative haemocultures at 54 days post infection, whilst 50% of those treated with benznidazole had positive results. Although both drugs were effective in reducing parasitism and inflammation in the heart, posaconazole-treated animals had plasma enzymatic levels of cardiac lesion that were indistinguishable from those of uninfected mice, whilst for benznidazole the enzyme levels were significantly higher than those of uninfected controls 31 days after the start of treatment. Posaconazole was more effective than benznidazole in controlling spleen enlargement and unspecific splenocyte proliferation in the early acute phase, but allowed higher levels of activation of CD4(+) and CD8(+) T-cells in the late acute phase when the adaptive immune response takes control of the infection. These results support the notion that posaconazole could be superior to benznidazole for the treatment of T. cruzi infection in humans.
Olivieri
Bianca P
BP
Laboratory for Innovations in Therapy, Education and Bioproducts, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil. olivieri@ioc.fiocruz.br
Molina
Judith Tibisay
JT
de Castro
Solange L
SL
Pereira
Mirian Claudia
MC
Calvet
Claudia M
CM
Urbina
Julio A
JA
Araújo-Jorge
Tania C
TC
D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000276:immunology / Q000517:prevention & control*; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000469:parasitology; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000473:pathology; D009593:Nitroimidazoles / Q000627:therapeutic use*; D016019:Survival Analysis; D014230:Triazoles / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000276:immunology
D000981:Antiprotozoal Agents; D009593:Nitroimidazoles; D014230:Triazoles; C101425:posaconazole; C009999:benzonidazole