Natural Resistance

Amphibians and birds are completely resistant to T. cruzi under natural conditions, and the reasons for this could give a clue as to how to manipulate human immunology to block this parasite. Amphibians and birds have an innate immunity. When infective bloodstream forms of T. cruzi are injected into chickens during experiments to attempt infection, the trypomastigotes are rapidly destroyed within one minute, scarcely enough time to become intracellular and reproduce as amastigotes and then change into infective trypomastigotes. When infective trypomastigotes are placed in fresh human blood or serum from other mammals in vitro they are not destroyed, and the parasite may remain alive for several weeks in vitro until antibodies are formed that activate complement. (Complement is a series of enzymatic proteins in normal serum that, in the presence of a specific activatorthe parasitedestroys the invader.) This delay provides enough time for T. cruzi to become firmly established in the mammalian host.

Experiments have shown that the natural resistance of birds to T. cruzi infection is antibody independent and related to complement. It is antibody independent because birds kill bloodstream forms immediately, before antibodies can form. Components on the surface of trypomastigotes activate complement in chickens but not in mammals. Proof that complement kills T. cruzi in chickens is provided by experiments in which cobra venom is used to destroy complement in chickens. In chickens treated in this fashion, the parasites stay alive for long periods of time, although they do not infect the chicken. Other factors may be involved that alter the parasites’ ability to survive, such as high body temperature of birds.

Complement in mammals is not directly activated by the parasites: such activation in these hosts is antibody dependent. That is, the only way that human complement will destroy T. cruzi is after specific antibodies have been formed against T. cruzi antigens and have attached to the surface of the parasite. Human complement is activated by a specific antibody bound to T. cruzi antigens; then its enzymes punch a hole in the parasite and kill it. Already discussed, the formation of effective antibodies is delayed for several weeks following introduction of the parasite, providing a window of time for T. cruzi to infect the person.

Humans appear to have no natural resistance to T. cruzi. Epidemiological factors, such as house hygiene, sleeping arrangements, and use of insecticides, explain the occurrence of uninfected individuals in highly endemic areas, but these preventative measures do not constitute natural resistance. The misconception of natural human resistance may arise from the fact that the host may respond differently to different strains of the parasite and that Chagas’ disease manifests itself in a wide variety of pathologies, creating the impression that certain people are more resistant than others. During the acute phase, some patients manifest mild symptoms or none at all; but, again, this may be due to differing strains of T. cruzi as well as to individual immune responses. In patients displaying relatively minor acute symptoms, seroconversion (in which a previously negative‑testing individual suddenly tests positive) documents that infection has taken place and that T. cruzi is moving slowly and surely. Therefore, significant factors that influence pathology are parasite strain and individual immune competence.

One other factor influencing pathology appears to be the length of time humans have been exposed to Chagas’ disease. As discussed in Chapter 2, Andeans in the highlands of Chile had a very high infection rate, but their cardiac involvement was lower than that detected in other endemic regions (González et al. 1995). Within this same region, scholars had earlier uncovered mummies of early Andeans from about A.D. 500 with clinical symptoms of Chagas’ disease. The more benign character of Chagas’ disease is explainable in the context of either the T. cruzi population circulating in the area and/or the ancient adaptation of the parasite to the human host in this area, particularly in the Andean highland.