intensity of fever), cardiac enlargement, hypotension, and heart failure (Andrade 1994, Koberle 1968:80). Heart alterations vary from slight to severe, as registered by electrocardiogram, but disappear after the acute phase (Borda 1981). Seventy percent of acute cases show no electrocardiographic or radiological abnormalities due to acute myocarditis of different stages (Laranja et al. 1956, WHO 1991:3). The remaining 30 percent indicate such electrocardiographic irregularities as sinus tachycardia, low QRS voltage, prolonged P-R interval, and primary T- wave changes. Chest x-rays can reveal cardiomegaly of varying degrees of severity.
About 2-3 percent of the acute cases with myocarditis die. Infants under two years constitute the greater number in this group. Also common to children of this age group is meningoencephalitis, another severe complication of the acute stage. Patients suffer convulsions, with or without fever, and lose consciousness to varying degrees (WHO 1991:3). The death rate for acute Chagas’ with meningoencephalitis can be as high as 50 percent (WHO 1991).
For the remaining cases, the symptoms subside spontaneously within one to two months, without clinical symptoms in the short or medium term. Sometimes the frequency of tachycardia is extremely high and continues to increase after the remission of the temperature during the recovery process (Koberle 1968:80).
For those who survive the acute phase or who do not experience it, death from subsequent acute phases is frequently prevented by the presence of the parasite and the complement immune system. This is referred to as partial immunity, and it is important to consider in attempts to destroy the parasite during initial attacks within the acute stagewhich may not be a good idea if the patient is to be subjected to new infections and subsequent violent acute phases. However, even with partial immunity over time, there is molecular mimicry between
Pathology of the Acute Phase
The pathology of the acute phase begins with an increase of trypomastigotes circulating in the blood (George Stewart, interview 2/21/92). During this phase, trypomastigotes can be detected in blood samples, whereas in later phases very few circulate and either serodiagnosis for antibodies or xenodiagnosis for circulating parasites is needed to test for infection.
Trypomastigotes spread through lymphatics, with resulting lymphadenopathy. Initially, trypomastigotes actively penetrate host cells, but they may also enter through phagocytosis by host macrophages, reproducing as amastigote forms (Schmidt and Roberts 1989:65). The trypomastigotes lose their undulating membrane and flagellum inside the host cell and begin reproducing by means of binary fissioneventually producing so many amastigotes that the host cell is ruptured and killed. Amastigotes form into cystlike pockets, called pseudocysts, within the muscle cells. Some amastigotes evolve into trypomastigotes and find their way into the bloodstream, where they are picked up by
The pathology of the acute phase is the least understood because the phase is very short and not everyone infected passes through it. As parasitologist George Stewart (interview 4/15/92) explains it: cellular response on the part of macrophages encapsulating trypomastigotes at the site of the bite results in inflammatory responses that set off the acute phase. The invasion by macrophages results in a cascade of events. One such event alters the immune system. During the acute phase there are dramatic alterations in macrophage and lymphocyte cell populations, along with T-cell and B-cell responses. Macrophages are antigen-presenting cells (APCs) that consume the antigen, partially digest it, and display its epitope and class-II protein on their surfaces. T-cells recognize the antigen’s epitope found on antigen-presenting macrophages and activate B-cells to produce plasma cells that secrete antibodies specific to the antigen. Throughout the acute infection period, parasites can be detected in most tissues, including trypomastigote forms in fairly large numbers. The sites of the growth are characterized by inflammatory cellular infiltrates. Wherever the parasite is growingin lymph nodes and locally in the skinmacrophages, T-cells, and B-cells massively invade these cells. This invasion does not continue into the chronic phase.
This pan-lymphocyte proliferation is accompanied by severe immunodepression-the immune system becomes exhausted and specific antibodies against the parasite are inadequately produced. Very few antibodies are produced against the parasite, because there is massive polyclonal non-specific B-cell stimulation. Suppression is achieved by polyclonal B-cell activation early in the infection; many subtypes of B-cells are stimulated to divide and to produce nonspecific IgG and autoantibodies (Schmidt and Roberts 1989, Kobayakawa et al. 1979).
The result is a random, nonspecific impact on the parasites. It acts more like a bombing in a blitzkrieg than targeting bombs with radar and aiming at a specific site. Suppression of the immune system is indicated to some degree by the fact that all this activity is ineffectual. Experimentally, chagasic antigens have been injected into the host during the acute phase of the disease, resulting in the nonresponse of antibodies to these antigens and further indicating the parasite’s ability to alter the immune system.
Experiments with mice indicate that if scientists destroy T-helper cells by injecting mice with T-helper cell antibodies, polyclonal B-cell activation will be stopped. This implies that such activation is T-helper-cell mediated and that trypomastigotes alter the T-cells; so it is not simply mitogenic stimulation of B-cells. As mentioned, acutely infected patients respond with a massive proliferation of B- and T-cells, but the T-cells don’t live up to their reputation and are deficient in their cytotoxic influence. Causing this are suppressor T-cells that are highly active during the acute phase and figure in the immunosuppression, but the major players are the macrophage subpopulations. When the trypomastigotes initially enter the body, antigens are consumed by macrophages that partially digest the antigen. The macrophages initiate cytokene communication that leads to enormous proliferation of T-helper cells and B-cells and that probably stimulates suppressor T-cell activity. T-suppressor cells interact with T-helper cells by dampening the immune response and by lessening the effect of cytotoxic cells, which have an effect opposite those of T-helper cells (Schmidt and Roberts 1989).
Researchers at IBBA in La Paz, Bolivia, also have been studying the pathogenesis of acute Chagas’ disease among high-altitude patients (Carrasco and Antezana 1991). They provide an alternative explanation: after the parasite penetrates the blood in the acute phase, it produces septicemia with hematogenous metastasis, which refers to the presence of
Maturation of trypomastigotes is uniform, but not all leave the cyst to become active at the same time. Maturity of the nascent trypanosomes requires adequate biochemical conditions. Mature trypanosomes return to the blood, where they circulate throughout the body searching out other cells to continue their cycle or to be picked up by
Other trypomastigotes remain in the cysts and self-destruct, leaving behind an array of toxic materials, dead parasitic material, pseudocysts, and destroyed cells that produce inflammations and tumors underneath the skin, such as chagoma and Romana’s sign. According to Carrasco and Antezana (1991), the inflammatory process is self-limiting and does not attack other organs. Other researchers, however, referred to in Carrasco and Antezana, indicate effects upon the central nervous system. Viana in 1911 described an alteration of ganglion cells and their disintegration corresponding to the velocity of broken pseudocysts within the central nervous system of acute patients (Breniere et al. 1983). Monckeberg mentioned in 1924 severe lesions of nerves and ganglions in the hearts of dogs experimentally infected with
