By 1980 Bertha’s heart rhythm had worsened, so Jáuregui implanted a pacemaker that same year, which was replaced in 1991. The pacemaker regulated her heartbeat and the fainting spells diminished, so Bertha was able to resume her work as a seamstress, although she suffered from minor fatigue when she climbed the streets of La Paz at 12,000 feet.
Most likely as a result of congenital infection, two of Bertha’s daughters also have heart problems. The eldest daughter, now thirty-eight, was born with heart trouble and suffers continual fatigue. After Bertha learned that Chagas’ disease was congenitally transmitted, she encouraged her daughter to undergo xenodiagnosis. Dreading being bitten by vinchucas, the daughter refused testing. She is afraid because the bites are irritating; alternative serological tests, such as ELISA Immunosorbent, are available in La Paz and are painless except for the drawing of blood. The second daughter has tachycardia and was tested by xenodiagnosis, with negative results (see Appendix 12).
Dr. Jáuregui has treated the symptoms of many patients suffering from heart diseases caused by chronic Chagas’ disease in the Thorax Hospital in La Paz. This hospital was built earlier this century and features high ceilings, tile floors, and tall steel beds, reminiscent of the nineteenth century when some diseases were believed to be caused by emanations from the earthmiasma theory. Jáuregui has claimed no cures for chronic Chagas’ disease and only treats its symptoms, as in the case of Bertha. As Jáuregui described it in an interview on July 19, 1991:
T. cruzi are muy listo (“shrewd critters”)! They circulate in the blood as little as possible, only to be transmitted. They inhabit cells of heart and intestines, vital areas where, to kill them, you have to destroy the organs. All I can do is help patients live a little longer by treating their symptoms. There is no cure for chronic Chagas’ disease.
Bertha’s case history is illustrative of that of many Bolivians who suffer cardiac problems from chronic Chagas’ disease. Ventricular tachycardia frequently occurs among patients of La Paz such as Bertha and is perhaps related to hypoxia (low oxygen) stress. La Paz is situated on slopes with elevations ranging from 11,000 to 12,000 feet. Infected chagasic patients continually climb up and down those slopes in the course of daily life, and for those with heart disease this is difficult and dangerous. Andeans are traditionally renowned for their strong hearts, extra lung capacity, and numerous red blood cells.
Until the recent epidemic of Chagas’ disease in Bolivia, heart disease was not considered the killer there that it is in the United States. However, with the increasing number of chronic chagasic patients, recent Bolivian studies indicate increasing electrocardiographic abnormalities characteristic of Chagas’ disease-related heart disease. Jáuregui and Casanovas (1987:30-33) observed a total of 4,108 patients throughout Bolivia and found 853 (20.8 percent) with cardiac abnormalities, out of which 436 (10.6 percent) were infected with Chagas’ disease. Pless and colleagues (1992) did a clinicoepidemiological study in the remote rural village of Tabacal in southcentral Cochabamba, Bolivia. They examined 153 out of 160 villagers for signs of Chagas’ disease and found that 116 people (76 percent) tested positive. The people infected with T. cruzi were 3.5 times more likely than uninfected people to have signs and symptoms of heart failure and nine times more likely to have electrocardiogram (ECG) abnormalities. Some 33 percent of ECG conduction defects occurred in adults over thirty-five years of age. Tabacal is similar to hundreds of other villages in southcentral Bolivia, which suggests that heart disease could be a major public health problem in this area (Pless et al. 1992, Weinke et al. 1988; see Appendix 10: Chronic Heart Disease).
Altitude appears to affect the manifestations of chronic chagasic heart disease. The lower levels of oxygen characteristic of high altitudes (hypoxia) place additional stress on chronic chagasic patients emigrating from lower to higher regions of the Andes. Patients with heart disease in La Paz are at greater risk of mortality than those at lower levels. The aerobic effect of living at high altitude, which traditionally endows Andeans with strong hearts, is counterproductive to individuals suffering with hearts afflicted with T. cruzi.
Therapeutically, patients with chronic Chagas’ disease stand a better chance of living longer at lower altitudes if they can avoid vinchuca bites, which intensify parasitic infestation of the victim’s body; furthermore, Trypanosoma cruzi has different strains, or zymodemes, which hypothetically possess different clinical manifestations (see Appendix 2: Strains of Trypanosoma cruzi). One advantage, already discussed, is that the victim is not likely to suffer another acute phase, which often is deadly.
Dr. Toro Wayar has studied and treated patients with chagasic heart disease in Sucre, Department of Chuquisaca, Bolivia, where he practices as a cardiologist and is director of the Centro de Investigación y Diagnóstico de la Enfermedad de Chagas-Sucre.[33] The Department of Chuquisaca is heavily infested with triatomine bugs and has a high number of infected chagasic patients. For eight years, Dr. Wayar and his staff have performed clinical and electrocardiographic studies of patients either diagnosed with or suspected of having Chagas’ disease. The following are excepts from an interview with Dr. Wayar on June 20, 1991:
The majority of our patients have positive serological indicators that they are infected with Chagas’ disease but totally lack clinical indicators by radiology or electrocardiography. We refer to these patients as infectados chagasicos [people infected with Chagas’ disease]. They become aware of being infected when they are examined for other reasons or they realize they have lived in endemic chagasic areas and want to see if they are infected.
A minority have clinical symptoms discovered in the cardiovascular system. They could have alterations determined by x-ray in the size of the heart or alterations in the heart rhythm determined by electrocardiogram. Concerning alterations of the heart size, when trypanosomes settle in the heart, they could affect all heart muscles, causing chronic inflammation of the myocardium [myocarditis]. The heart becomes structurally disorganized in all the muscular fibers; it increases in size and presents different degrees of malfunctioning, depending upon the grade of increase, which can be anywhere from two to three times its normal size. But this is infrequent because the person seldom survives to this stage.
The more common type of alteration is found when trypanosomes damage the electrical system of conduction of the heart, which controls the number and intensity of heart beats. Trypanosomes could alter any sector and cause many variations in the form of arrhythmias. This is a characteristic particular to chronic chagasic patients. Arrhythmias range from very light to very severe, which can cause sudden death (muerto subito). Treatment for these patients is limited to resolving cardiac problems, with rather unsuccessful treatments for ridding patients of trypanosomes. (Toro Wayar, interview 6/20/91.)
Dr. Wayar questioned the fact that trypanicides were able to rid chagasic patients of trypanosomes, and there is considerable debate concerning this. Even if the patient can be rid of T. cruzi, that would not eliminate the immunological consequences of the original infection (see Appendix II: Immune Response).
An important conclusion of Toro Wayar is that electrocardiographic abnormalities were found in lower percentages than was commonly thought. He attributed this to strains of T. cruzi infecting the colons of patients rather than their hearts. Wayar’s conclusion supports the adaptive ability of T. cruzi strains to select intracellular locations that promote their reproductive process. As in La Paz, heart disease is especially lethal in Sucre because of hypoxia, and it is only natural that strains of parasites that reside in the colon have a longer time to reproduce than those in the heart, which die off with their hosts.
Apparently this reasoning runs counter to the findings of Jáuregui and Casanovas (1987:30-33), who reported a higher incidence of heart disease in mesothermic regions than was typically found in tropic zones. It does suggest that many chronic chagasic patients with heart problems in La Paz were infected at lower altitudes and later moved to La Paz. The resulting hypo
xic stress then interacted with chagasic heart disease to produce ECG abnormalities.
As already mentioned, natives of higher altitudes have developed physiologically to hypoxia and have well-adapted cardiovascular systems to deal with the resulting low-oxygen stress. Conversely, peasants migrating from the lowlands to higher altitudes lack these adaptive features and, if they become infected with Chagas’ disease, they are at greater risk for heart problems because they are unaccustomed to hypoxic stress, which interacts synergistically with chronic myocarditis. One advantage these migrant lowlanders have in living in La Paz is the decreased possibility of reinfection with additional parasites or new strains brought about by vinchuca bites. Thus, verticality, or people living at different altitudes in Bolivia, adds additional complexity to chronic Chagas’ disease in this country.
Although cardiopathy is frequently associated with chronic Chagas’ disease in Bolivia, this disease also manifests itself in other organs of the body, possibly as a function of strain diversity within T. cruzi the organisms adapting to host physiology and hypoxic stress. As living organisms, T. cruzi and humans establish parasitic relationships that dynamically vary with environmental stresses. By the time the patient is chronically ill, these parasites have become established in human organs, where they have had ample time to reproduce. It is often environmental stresses, such as moving to higher altitudes, or compromised immune systems that eventually destroy the host.
Chronic heart disease is treated symptomatically, with emphasis placed on the cardiovascular aspects. Bolivian doctors also recommend benznidazole or nifurtimox to prevent the spread of parasites from tissue to tissue, but these trypanocides are questionable with regard to their effectiveness against intracellular parasites in the amastigote form (Gutteridge 1982, 1985; Brener 1975, 1979; see also Appendix 13: Chemotherapy).
The Burden of a Weakened Heart in the Andes
Very few Bolivians with chagasic heart disease (.01 percent) are as fortunate as Bertha in being able to have pacemakers installed and to be treated by an expert doctor. Acquired in her infancy, Chagas’ disease has left Bertha with irreversible heart damage: arrhythmia (irregular heartbeats) and bradycardia (slow heartbeats), which could lead to heart failure or sudden death without the help of a pacemaker. Many Bolivians have no medical insurance. Pacemaker implantation costs about U.S. $3,000 per person in Bolivia, prohibitively expensive where the average income is U.S. $580 per person per year. No drug exists to reverse these patients’ chronic condition, because of the immunological consequences of the original infection. Many victims are farm or mine workers who are unqualified to find lighter jobs. They have little alternative but to continue work and face the daily prospect of their hearts failing to pump enough blood through their bodies to keep them alive. Chagas’ disease can seem especially cruel to these workers: when they are supposed to be at the strongest phase of their lives and most able to support young children, they are debilitated and unable to work as hard.
The socioeconomic impact of the disease during the chronic stage is high, as data from Bolivia show: about 25 percent of the infected population (1,500,000 people) will develop severe cardiac and digestive lesions such as cardiac arrhythmia (215,000) and megaesophagus and megacolon (150,000; see Valencia, Jemio, and Aguilar 1989).[34] In 1992, the indirect costs of lost production in Bolivia due to Chagas’ disease morbidity and mortality amounted to $100 million, and the direct cost for Chagas’ disease treatment reached $20 million (SOH/CCH 1994). The collective biomedical cost for pacemakers and corrective surgery at $3,000 per person would run about $1 billionastronomically unfeasible in Bolivia as well as in other Andean countries. Put another way, this is enough for the improvement or construction of a million rural dwellings at a minimum estimated cost for each of U.S. $1,000. Data from Brazil are equally grim, with 45,000 cases of cardiac arrhythmia and 30,000 cases of megaesophagus and megacolon estimated annually, with the collective cost at about U.S. $225 million per year (Special Programmes 1991 Report).
In the Andes, chronic Chagas’ disease debilitates Andeans who have evolved with strong hearts adapted to the low oxygen of higher altitudes. Highland Andeans have an extra pint of blood in their bodies and larger lungs to accommodate the 20 to 30 percent less oxygen at levels between 9,000 and 16,000 feet. Climbing up and down hills and mountains, Andeans have enjoyed the aerobic effect that daily exercise provides runners. Chagas’ disease has not been particularly prevalent at higher altitudes because vinchucas prefer warmer and more humid climates. However, this has drastically changed with the massive migration of infected Bolivians and vinchucas to practically every site in the Andes. Because of layoffs in the mines, droughts, floods, and increased cocaine production, peasants seasonally travel to endemic areas, where some become infected with T. cruzi and bring it and vinchucas to other regions. Lowland peoples have also spread this disease to highland Andeans through blood transfusions.
Pathology of Chronic Disease
Chronic manifestations usually take three formsin order of prevalence: cardiac, colonic, and esophagealand more than half of the patients with Chagas’ disease reveal abnormal electrocardiograms. Up to 30 percent of people with the indeterminate or inapparent form of the infection suffer from cardiac, digestive, or neurological damage ten to twenty years after having contracted the disease, while the remainder never exhibit any manifest organ involvement (WHO 1991; see Figure 8). Symptoms of chagasic heart disease progress from barely decipherable indicators, such as fever, anemia, and hypertension, to serious pathologies.[35] Cardiomegaly results in the heart enlarging five or six times its normal size; but it is not found in all chronic patients, such as Bertha, whose symptoms of Chagas’ disease were expressed by ventricular arrhythmias, which frequently cause death sooner than does cardiomegaly.[36] Heart disease illustrates how widespread the damage of Chagas’s disease can be and how difficult it is to diagnose this disease by means of only a specific set of symptoms.
The pathology of the chronic stage of Chagas’ disease is related to denervation within the nervous system of the colonized organ (Brener 1994). Degeneration of neurons in the heart’s parasympathetic ganglia is common in chagasic patients with heart ailments. With megacolon and megaesophagus, lesions of the colon and esophagus are caused by destruction of nerve cells. These lesions are jointly caused by the parasite (intracellular invasion of the trypomastigotes, encystation of amastigotes, and bursting of cells) and by the autoimmune response of the host. Increasing evidence indicates that the pathogenesis of Chagas’ disease is related to the parasite’s ability to manipulate the host’s immune system.[37] It has been found that people die from chronic manifestations in which lesions are left from T. cruzi but the parasite is not present, perhaps being lysed at an earlier stage. This has led scientists to suspect that the traces or lesions left from the parasite mimic human antigens. The immune system mistakes these human cells as epitopes from T cruzi and attacks them (discussed in Appendix ii). This is similar to rheumatic fever, where people die from the disease long after the pathogen has been removed.
During the acute phase, inflammation, fevers, and cell damage are related to overactivity of the lymphocytes (see Appendix 9). This polyclonal stimulation is triggered by macrophages devouring trypomastigotes. Results include violent onslaughts on the parasites that drive them into central nervous system cells, lysing cells encapsulated with parasites that release toxins into the body, ineffective destruction of antigens, and eventual weakening of immune response. In short, damage from acute Chagas’ disease is more a result of overactivity of the immune system than damage due directly to T. cruzi.
The cardiopathy of chronic Chagas’ disease is an issue of considerable debate, with several lines of evidence to account for, including the inability to consistently find parasites in damaged areas (Torres 1930). The passive transfer of heart lesions by CD4+ T cells from T. cruzi-infected mice to uninfected mice indicates that inflammatory heart lesions could be of an autoimmune nature (Andrade 1958,
Ribeiro-dos-Santos et al. 1992). (In simpler terms, the T cells from infected mice were encoded with self-destructive tendencies, and when these T cells were placed in uninfected mice, they caused damage as if the sterile mice had the parasites.)
Referred to as the antigenic mimicry hypothesis, lymphocytes in the heart recognize and mount delayed-type hypersensitivity responses toward a tissue-specific heart component bearing structural similarities to a given T. cruzi antigen.[38] A recent study indicates that heart-tissue destruction in chronic Chagas’ disease may be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after T. cruzi infection (Cunha-Neto et al. 1995). Indirect evidence suggests that there are antigenic cross-reactions between T. cruzi and heart tissue. Myosin heavy chain (myosin HC) is the most abundant heart protein—50 percent of total protein by weight—and is recognized in heart-specific autoimmunity in rheumatic heart disease (Neu, Beisel, et al. 1987). Research indicates the involvement of cross-reactions between cardiac myosin and a recombinant T. cruzi protein (B13) as targets for attack by the victim’s T cells (Cunha-Neto et al. 1995).[39]
The immune response is also impaired in the chronic stage of Chagas’ disease (see Appendix II: Immune Response). An improper response of the cellular immune system results in tissue damage, which might lead to the autoimmune cardiac and neural damage of chronic T. cruzi infection (Botasso et al. 1994). Trypanosoma cruzi infection impairs immunity to many antigens and mitogens.[40] Chagasic patients have a reduced cellular immune response to common mycobacteria antigens, such as those of tuberculosis and leprosy (Bottasso et al. 1994).[41] T. cruzi causes loss of the TH1 response to mycobacterial antigens.
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