The Kiss of Death

trypomastigotes and that would act locally or at short distances (Pereira Barreto 1985, Koberle 1970). The fact that approximately 80 percent of the ganglion cells could be destroyed in the acute phase constitutes the fundamental revelation of Koberle’s neurogenesis theory (Koberle 1970). However, first Andrade in 1958 and later Dominguez and Suarez in 1963 did not find a similar correlation in their experiments (Carrasco and Antezana 1991).

According to neurotoxic theory, it is the trypomastigotes that remain in the pseudocysts and self-destruct that produce the toxic materials within the tumors and cause the inflammations. T. cruzi alters cell permeability and thus dramatically increases calcium levels that are toxic to human cells. The parasite needs high levels of calcium for its own cytoplasm, but extra calcium alters cell metabolism and could explain some of the cellular necrosis (George Stewart, interview 2/4/94).

A more scientifically acceptable theory holds that damages during acute phases are due to an overreaction, as well as ineffective reaction, of the autoimmune system (see Brener 1994). Pathogenesis during the acute phase is the result of a cascade of events involving the immune system in which panlymphocyte proliferation is accompanied by a severe immunodepression: the immune system becomes exhausted and specific antibodies against the parasite are inadequately produced. The fact that the human immune system is implicated within the pathogenesis indicates, as in AIDS, the deficiencies of the human body’s defenses against viruses and parasites and the need for more research into the complexities of the immune system and how it sometimes becomes our own worst enemy. Simplistic theories of antigens and antibodies have been replaced by complex synergetic interactions of events and cascades of events between complex parasitic and human immune systems.

When symptoms of Chagas’ disease appear among patients in endemic areas, health workers should test for acute Chagas’. At this stage, parasitological examinations are more easily performed because T. cruzi are circulating in the blood and can be observed in drops of blood examined under the microscope. Antibodies are also in high number, assisting in the detection through use of ELISA immunosorbent assay. Xenodiagnosis is often necessary during indeterminate and chronic stages of the disease because parasites circulating in the blood are fewer in number. As discussed, in contrast to other means of testing such as through extraction of blood in a syringe, xenodiagnosis uses sterile vinchucas to feed in the armpit of the patient for thirty or more minutes, providing the bugs with time to ingest T. cruzi and blood. It is often difficult to catch T. cruzi in the bloodstream because its natural habitat is intracellular. Xenodiagnosis can also determine the zymodeme and population size of T. cruzi, which is important for treating latent and chronic stages. (See Appendix 12.)

Detecting Acute Stages

In endemic areas of Chagas’ disease it is important to detect acute and even asymptomatic infections in children so that specific therapy can be started immediately. Serologic profiles of eighty-six chagasic children and fifty-six healthy children from a highly endemic area in Cochabamba, Bolivia, indicate that alpha-2-macroglobulin (A2M) and C-reactive protein (CRP) were significantly increased in acute chagasic children (MedranoMercado et al. 1996). Because parasites are commonly present in blood and tissues during the acute phase, it is possible that the high levels of A2M may act as inhibitors of a high level of proteinases, derived from the parasites, from host cell damage, or from both. These results open a route to discern different stages in the acute infection by examination of sera and using humoral criteria:

1) an early acute stage, with an increase only in specific anti-T. cruzi immunoglobulin M (IgM) levels (group 1);

2) an intermediate acute stage having high specific IgM levels and/or high immunoglobulin G (IgG) levels and/or high anti-galactose (anti-Gal) levels and increased A2M and/or CRP levels;

3) a late acute stage, with low IgM levels but high A2M, CRP, anti-Gal, and specific IgG levels.

The detection of high immunoglobulin G alone is indicative of the chronic/indeterminate stage of Chagas’ disease (Medrano-Mercado et al. 1996).

In Bolivia, however, serological methods involve many problems, including difficulties in sample collection and storage until the time of screening; difficulties in the standardization of the diagnostic methods commonly used, such as the indirect hemagglutination test, the indirect immunofluorescence test, ELISA, or complement fixation; and the absence of a clear correlation of the results of tests performed in different laboratories (Pless et al. 1992). The procedures and techniques to quantify five relevant proteins are easy to perform and to automate for large-scale screening, in contrast to other immunologic techniques that are used for serodiagnosis of Chagas’ disease. They would consititute a tool in detecting acute Chagas’ disease, especially in endemic rural areas.

APPENDIX 10 Chronic Heart Disease

Symptoms of chronic Chagas’ disease are insidious and progressive (see Figure 8). After recovering from acute phases, many people, perhaps the majority, remain asymptomatic for the rest of their lives, while others remain in good health for many years before developing symptoms and signs of the chronic stage of disease. The chronic phase is characterized by widespread damage to the organ(s) and the multiform chagasic syndrome, with its digestive (aperistalsis, megaesophagus, megacolon), respiratory (megatrachea, bronchiectasis), urinary (megaloureter), cardiac (denervation), and neurological (myelopathy, encephalopathy) components (Koberle 1968, Iosa 1994).

Cardiac abnormalities range from types of rhythm disturbances to various forms of heart block, including right- and left-bundle branch block, hemiblocks and atrioventricular blocks (see Andrade 1994, Iosa 1994). Some tested patients show a normal electrocardiogram (ECG) reading, particularly in the early stages, but stress testing may reveal ECG abnormalities such as heart block or arrhythmias which might not be seen in resting ECGs. Sometimes available in urban centers, echocardiography may also be useful in evaluating cardiac chamber size and left-ventricular function and in following the progression of the disease.

Although electrocardiographic abnormalities related to Chagas’ disease have been estimated as high as 87 percent (Hurst 1986:1170), 33 percent seems a more reasonable figure from studies in Brazil. Almost one-third of 2,000 subjects examined by ECG in endemic areas of Brazil indicated abnormalities, and 9 percent of chest x-rays showed enlargement of the cardiac shadow (Braunwald 1988:1447; Hurst 1986:1170).

Pedro Jauregui and Alberto Casanovas (1987:30-33) analyzed electrocardiographs from people living in endemic chagasic areas throughout Bolivia to see how many indicated electrocardiographic abnormalities characteristic of chagasic-related heart disease. They studied 4,108 electrocardiographs from patients of rural communities in the Departments of La Paz (280), Tarija (258), Potosi (311), Cochabamba (1,818), Santa Cruz (1,185), and Chuquisaca (256). They found that 436 (9.4 percent) strongly indicated Chagas’ disease from the total number of 853 (20.8 percent) of ECG abnormalities. Of the 853 total abnormalities found, 469 (55 percent) were in men and 384 (45 percent) were in women, with 761 (89 percent) being adults and 92 (11 percent) being youths.

Criteria used to indicate chronic chagasic myocarditis among the ECG abnormalities were left anterior hemiblock (29 percent), block of the right bundle branch (27 percent), and sinal bradycardia (16 percent). There were 152 patients who had combined abnormalities of block of the right bundle branch and left anterior hemiblock. Including other abnormalities, 61 percent suffered from heart block, 22 percent from arrhythmias, 10 percent from repolarization disorders, 2 percent from overcharges, and 2 percent from other alterations. Youths indicated light disorder of conduction of the right bundle branch or sinal bradycardia with repolarization suggestive of vagotonia. Vagotonia is a disorder that results from overstimulation of the vagus nerve, causing a slowing of the heart rate,