Side effects of immunization with live attenuated Trypanosoma cruzi in mice and rabbits

Abstract

Immunity against lethal, bloodstream forms of Trypanosoma cruzi was achieved in mice by preinoculation of ≃105 culture epimastigotes of an attenuated T. cruzi strain (TCC). The risks of TCC inoculation in terms of pathogenicity or eventual increase in virulence of TCC progeny were evaluated No pathogenic parasites could be selected from TCC progene by either mouse, triatome, or culture passages. Immunizing doses of live TCC did not induce in adult mice alterations resembling chronic Chagas' disease, as judged by patterns of mortality, tissue damage, autoantibodies, or parasite recovery. On the basis of the same criteria, however, a remarkable similarity could be established between the disease caused in mice by inoculation of low numbers (102) of pathogenic trypomastigotes and human chronic Chagas' disease. Although patent parasitemias were never revealed in fresh blood mounts obtained from TCC-inoculated mice, a few hemocultures and xenodiagnoses gave positive results, particularly soon after inoculation at birth. The parasites recovered by either method remained in the attenuated, epimastigote stage. In rabbits, no local lesions, fever, weight loss, or histopathological alterations were detected after subcutaneous inoculation of 107 TCC organisms, although one fifth of the animals yielded positive hemocultures of epimastigotes. The contrasting host response to cultured epimastigotes as compared with blood trypomastigotes indicates that, in experimental Chagas' disease, immunoprotection is not necessary associated with immunopathology.