The Kiss of Death

fainting, and dizziness.

Diagnostic tests were not given to verify what percentage of these people were infected with T. cruzi, so conclusions are indefinite; however, some hypotheses can be suggested, such as the relationship of altitude to chagasic heart disease. Altitude appears to affect the manifestations of chronic chagasic heart disease. Lesser oxygen intake at high altitude (hypoxia) puts additional stress on chronic chagasic patients emigrating from lower to higher regions of Bolivia. Twenty-three percent of ECG alterations were found in patients from mesothermic zones as compared to 14 percent from those in subtropical zones. Mesothermic zones in Bolivia are mountains, plateaus, and valleys at altitudes from 8,000 to 14,000 feet. Although triatomine vectors are infrequently found above 13,000 feet, Bolivians move from the lower areas where they were infected to higher altitudes where hypoxia combines with chagasic stress to produce ECG abnormalities.

Although research is needed to correlate the incidence of ECG abnormalities with seropositive chagasic patients in higher altitudes, one clinical conclusion is that patients with myocarditis in La Paz are at greater risk than those at lower altitudes. The aerobic effect of living at high altitude that has traditionally endowed Andeans with strong hearts is counterproductive to Andeans suffering with hearts infected with T. cruzi. Traditionally, Andeans have referred to leishmaniasis as “el mal de los Andes”; it now appears that Chagas’ disease may be the curse of Andeans.

Therapeutically, patients with chronic Chagas’ disease stand a better chance of living longer at lower altitudes if they can avoid becoming superinfected. However, at lower altitudes there is a greater risk of superinfection, as there are more vinchucas and infected people. This leads to an auxiliary research question: to what degree does superinfection precipitate chronic Chagas’ disease myocarditis among lowland Bolivians? Apparently, it has a limited negative effect, considering that only 14 percent of patients from mesothermic zones had ECG abnormalities.

APPENDIX 11 Immune Response George Stewart, coauthor

The human immune response to T. cruzi infection is inadequate and complex, providing at best partial protective immunity during the chronic phase and at worst causing severe immunopathology which may play a significant role in the morbidity and mortality rates of the disease. Pathology associated with T. cruzi includes immunopathology, an inflammatory response that causes chronic myocarditis and degeneration of the heart and gastrointestinal system. Even more insidiously, T. cruzi immunizes humans to their own antigens so that defensive antibodies become offensive and destroy myocardial and neural cells. As one favor, T. cruzi provides chronically infected patients with immunity from acute infections, but only as long as T. cruzi is present; it is as if to say: “Without me, you’re subject to acute infection from another bite!”

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 (Gonzalez 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.

Acquired Resistance to the Acute Phase

Although human hosts have no natural resistance to the acute phase of Chagas’ disease, infected humans usually acquire resistance to the severe pathology of the acute phase from subsequent infections, either of the same or different strains. Acquired resistance (partial immunity) is an immunity that slowly develops after the establishment of the acute phase and is antibody dependent. Acquired resistance primarily protects hosts from the mortality associated with initial contact with the parasite (acute phase) and from consequences of future acute phases by a quick and vigorous immune response. But acquired resistance remains only as long as T.