Figure 3.
Triatoma infestans.
Barbeiros have six strong legs, an inch-long body covered with fragile, transparent wings, bulbous eyes, and a proboscis nested under its body that can extend downward to ingest blood from mammals, including humans. Brazilians call these triatomine insects barbeiros, from the Portuguese word for barber, indicating that these insects cut like a barberreferring not to the fact that barbers accidentally cut the face with razors but that they also practice bloodletting, done at the time for medical purposes. Barbeiros are scientifically classified as Triatoma infestans (see Figure 3).
Carlos Chagas observed that barbeiros are sensitive to light and during the day hide in cracks and crevices of walls and ceilings where they rest, copulate, and lay eggs, which are tiny, white, and ball-shaped. Barbeiros are considered vampire bugs; they become active at night, descend from nests, are drawn to warmth, and draw blood from animals and humans. Faces are attractive targets that barbeiros pierce with their needle-sharp proboscises. They inject anesthetic and anticoagulant fluids that enable them to leisurely ingest blood from unwary and tired victims. Sleepers sometimes awake and smash the barbeiros, exploding the blood on their bodies or other surfaces as the bugs sluggishly return to their nests. They are superb crawlers and can attack victims by crawling beneath mosquito netting or from inside mattresses.
People also refer to barbeiros (or vinchucas) as “kissing bugs” because of their predilection for the face. Chagas called the resulting chagoma (carbuncle sore) from a bite beneath the eye Signo de Romaña and pointed this out as an important diagnostic indicator of acute Chagas’, discussed more in Chapter 4 (see Figure 4).
Figure 4.
Child with Romaña’s sign, a chagoma that occurs at the site of the bite from the vinchuca bug. This occurs during the acute phase in about one-fourth of those infected with T. cruzi. (Photograph from the Pan American Health Organization)
Barbeiros (vinchucas) are triatomines, with more than 100 species that are vectors of Trypanosoma cruzi. Triatoma infestans is the most widespread and effective species vector of T. cruzi in Bolivia, and Bolivians refer to it as vinchuca. Sometimes classified as reduviid bugs, barbeiros do not have the painful bite of other reduviids. Barbeiros have injector-needlelike snouts or noses that fold back under their bodies and protrude down, like half-opened jackknives, to pierce the victim’s skin. They can engorge more blood than their body weight, and when they defecate they can leave small blotches of tobacco-like stains on the skin. They need blood meals, one for each of five instar (life) stages, in which they transform from barely the size of a flea to that of a small cockroach. At the final, adult stage, they grow wings, copulate, lay eggs, and die. Rather simple in their needs, triatomine insects need only a place to hide during the day and mammals to feed on during the night. (See Chapter 4 and appendices for more on triatomines).
Lassance was infested with barbeiros because of its impoverished socioeconomic conditions and human intrusion into nearby forests. Triatomines were driven from their native habitats as railroads expanded. Crawling aboard railway cars, barbeiros followed westward expansion across Brazil. Many houses for humans were made of thatched roofs and adobe walls, with cracks, crevices, and cornices providing nesting sites for barbeiros. Carlos Chagas recognized the impact poverty has upon the spread of insects, parasites, and disease, something Walter Reed also had observed in regard to malaria.
Years earlier, Charles Darwin had also been fascinated by vinchucas, and it could be wondered if Darwin’s fascination augmented Chagas’ curiosity about these bugs. Both shared essential ingredients of successful fieldworkers, curiosity about certain creatures and how they relate to other creatures. It is likely that Carlos Chagas, like most classically trained biologists at the time, had read about vinchuca bugs in the Diary of the Beagle, written by Darwin on March 26, 1835:
We crossed the river of Luxan (Andean region of Mendoza)… At night I experienced an attack, & it deserves no less a name, of the Benchuca, the great black bug of the Pampas. It is most disgusting to feel soft wingless insects, about an inch long, crawling over ones body; before sucking they are quite thin, but afterwards round & bloated with blood, & in this state they are easily squashed. They are found in the Northern part of Chili & in Peru: one which I caught at Iquiqui was very empty; being placed on the table & though surrounded by people, if a finger was presented, its sucker was withdrawn, & the bold insect began to draw blood. It was curious to watch the change in size of the insects body in less than ten minutes. There was no pain felt.This one meal kept the insect fat for four months; In a fortnight, however, it was ready, if allowed, to suck more blood. (Darwin, in Keynes 1988:315)
Several years later, Darwin wrote in his zoology notebook at Edinburgh (1837-1839) a partial description of vinchucas in French, which I translate: “Vinchucas or Benchucas. The individual wings can be (four) five lines [lignes] long and they fly.” Darwin had found this quote from an earlier description by the naturalist Azara (1809, I:208-9): “La vinchuca [is] very annoying for those who travel from Mendoza to Buenos Aires… It is a beetle or scarab, whose body is oval and very flat, and who becomes fat like a grain of raisin, from the blood which he sucks. This insect only comes out at night. The individual wings can be five lines [lignes] and they fly, at least the large ones.”[5] He was referring to the fact that vinchucas grow wings only at the adult, or fifth instar, stage.
Darwin’s Disease
Experimentally, Darwin allowed vinchucas to draw blood from his finger and marveled at the dexterity of their proboscises. Some scholars have interpreted this to suggest that he became infected with T. cruzi, which would explain his semidebilitated state five years after the Beagle landed.[6] Several weeks after being bitten, Darwin wrote in his diary for April 9, 1835: “From this day till I reached Valparaiso, I was not very well & saw nothing & admired nothing” (Keynes 1988:323). Darwin reached Valparaiso on April 17. The incubation period corresponds to the lead time for acute Chagas’ disease, but nine days is relatively short for its duration.
A second indication is that several years after the vinchuca bite Darwin began suffering a complex of symptoms from an undiagnosed chronic illness. Chagas’ disease gradually develops into a chronic phase, what has been called an intricate lifelong minuet that is danced by the parasite and the host’s immune system (Goldstein 1989). This could explain Darwin’s illness: nonspecific symptoms of increased parasitemia such as malaise, fever, fatigue, and decreased energy when the immune system was down. Advancing age, periodic illnesses, psychological stress, and exhaustion could certainly have weakened Darwin’s immune system, which was necessary to keep T. cruzi at bay.
At the age of thirty-three, Darwin’s period of great physical activity was over. Darwin logs continual, nagging complaints in his diaries from 1839 until his death in 1882 that indicate a persistent and not readily diagnosed problem:
the smallest exertion is most irksome… periodic vomiting… I was almost quite broken down, head swimmy, hands trembling and never a week without violent vomiting… very weak… only able to tolerate short walks… headaches… fatigued… oppressed.. .flatulence… prolonged spells of daily vomiting of “acid & slime,” fright… sinking sensation… trembling… shivering… and fatigue. (Darwin, in Goldstein 1989)
These symptoms waxed and waned throughout Darwin’s life and greatly curtailed his professional activities, travels, and social life. In 1882 Darwin developed myocardial degeneration which progressed to angina pectoris; he died that year.
Some facts, however, work against the idea that Darwin died from Chagas’ disease. Darwin’s illness in many ways is not characteristic of Chagas’ disease. Darwin never mentioned the first signs of the acute phase, development of a chagoma, a rash consisting of tiny red spots, fever, and spleen and heart problems. However, the majority of afflicted adults (60 to 70 percent) do not suffer symptoms of the acute phase. Ignorance of this factor remains a problem because many infected individuals
with chronic Chagas’ disease claim they are not infected since they did not suffer symptoms of the acute phase. Chagas’ disease is frequently asymptomatic until years after the initial infection. The observation that Darwin reported no high fever is not sufficient in itself to rule out Chagas’ disease.
Exhibiting limited knowledge, Browne (1995:280) refers to Chagas’ disease as a South American sleeping sickness, with the implication that because Darwin did not suffer a fever typical of African sleeping sickness he did not have Chagas’ disease. American trypanosomiasis (Chagas’ disease) and African trypanosomiasis (African sleeping sickness) are both caused by trypanosome parasites: one by Salivaria, which lives in the saliva of its vector insect, and the other by Sterecoria, which lives in the feces of its vector insect. The difference between these parasites is that African trypanosomes remain in the blood and cause recurring fevers that exhaust the immune system; in contrast, American trypanosomes enter the neuron cells and frequently do not trigger immediate action of the immune system. American trypanosomes also reenter the blood.
Although Darwin’s symptoms did not indicate heart disease until he was seventy-one, a relatively long life for the nineteenth century, he could have suffered subtler degrees of myocardial dysfunction, associated with T. cruzi, causing many of the complaints listed in his correspondence (see Adler 1959; Medawar 1964; Goldstein 1989). This debate has brought attention to Chagas’ disease, sometimes referred to as Darwin’s disease, and its diffuse nature and complex symptoms. Some hope that Darwin’s body will be exhumed and its tissues examined for T. cruzi.
Discovering the Parasite
Darwin studied evolution from simple to complex creatures; Chagas studied how simple organisms destroy complex organisms. Chagas examined barbeiros which he collected. In sunlight he dried them and dissected their intestines, eventually finding some flagellates inside the lower intestines (see Figure 5).
Flagellates are protozoa, unicellular creatures that usually reproduce asexually and have flagella, or hairlike whips, propelling or pulling them. There are about 66,000 documented species of protozoa, with about half being represented in fossils; of the living species, about 10,000 are parasitic (Katz, Despommier, and Gwadz 1989). Unlike most of the helminths (worms), parasitic protozoa reproduce within the host to produce hundreds of thousands of individuals within a few days. They can pose major problems to human existence, causing malaria, giardia, vaginitis, amoebic dysentery, Toxoplasma gondii, African sleeping sickness, leishmaniasis, and pneumonia, among other ailments.
Chagas observed the newly found flagellates with the microscope, making fixed and stained microscope preparations, hoping to recognize the species or be able to characterize it as a new one. He observed that the parasite possessed a different morphological aspect than Trypanosoma minasensi, already recognized in Brazil, although it was a trypanosome, characterized by the undulating membrane, the large size of its basal body, or centriole, an organelle for cell division, and its undulating flagellum.
Chagas correctly identified the flagellated protozoan as a member of the family of trypanosomidae, but he believed it to be a previously undescribed genus and species. He named it Schizotrypanum cruzi: “in tribute to the master, Oswaldo Cruz, to whom I owe everything in my scientific career, and who guided me in these studies toward wide horizons, an adviser at any moment, a spirit of light and kindness, always quick in giving me the benefits of his knowledge and protecting me in the greatness of his affection” (in Kean 1977). (Oswaldo Cruz would also be memorialized by the founding of the Instituto Oswaldo Cruz, a world-renowned research center of tropical diseases in Brazil.) Schizotrypanum cruzi was later reclassified as Trypanosoma cruzi because it fits better into the genus of trypanosomes (see Chagas Filho 1993:85).
Figure 5.
Forms of T. cruzi: n = nucleus, k = kinetoplast, um = undulating membrane, f= flagellum. (See Appendix 1.)
Once Chagas had found T. cruzi, he still wasn’t sure that this parasite inhabited humans or other mammals, or that it caused the “strange disease.” Countless parasites are beneficial to humans; it was even possible that T. cruzi curtailed the reproduction of vinchucas. Hypothetically, Carlos Chagas reasoned that his Schizotrypanum cruzi was either natural to barbeiros, creating no sickness, or that the flagellates found in the gut of barbeiros represented one stage of a transforming parasite that passed over to mammals and caused the reported symptoms in Lassance. Consequently, he examined tissues of animals and humans who had died from this “strange disease” to see if they were infected with T. cruzi.
Another clue for Chagas was that Trypanosoma cruzi resembles Trypanosoma brucei gambiense, a flagellate protozoan that lives in the blood of cattle and humans, causing African sleeping sickness. Uninfected tsetse flies bite cattle and humans infected with T. b. gambiense, which are frequently asleep during the middle of the day (hence the origin of the disease’s name) and ingest the parasite. The parasite transforms into a metacyclic trypanosome in the saliva of the fly; from there it moves on to another host. Using plasmodia and trypanosoma parasites as models, Chagas suspected that T. cruzi had a similar cycle between barbeiros and mammals, causing yet another disease within them. He suspected that because T. cruziwas found in the rear gut of barbeiros, it was passed through the insect’s fecal matter to humans after the insect bit and then defecated near the wound. The parasite then entered through the bite wound.
In April 1908 Chagas spent the night in a house where he found a sickly cat, which he examined, finding T. cruzi. Two weeks later, he again visited the same house to treat a three-year-old child, Rita, feverishly ill. He found a large swarm of insects biting the inhabitants, including Rita, who had been healthy during his earlier visit. After he examined her blood, he found “the existence of flagellates,” as Chagas (1922) described it, “in good number and the fixing and staining of blood films made it possible to characterize the parasite’s morphology and to identify it with Trypanosoma cruzi.”
Rita had a fever of 40°C (105°F) for two weeks. Her spleen and liver were enlarged and her lymph nodes were swollen. Most noticeable to Chagas was a generalized infiltration, more pronounced in the face, and which did not show the characteristics of renal edema but rather of myxedema. Carlos Chagas (1911) found this last symptom to be one of the most characteristic forms of the acute stage of the disease; it revealed some functional alteration of the thyroid gland, perhaps affected by the pathogenic action of the parasite.
Three days later, Rita died from parasitemia caused by T. cruzi. Today, some ninety years after Rita’s death, seven children die each day from the acute phase of Chagas’ disease in Bolivia (Ault et al. 1992:9). Carlos Chagas also treated another patient in 1908, a woman named Bernice, who died in 1989 still harboring the parasite but with no evidence of pathology (Carlos Chagas Filho 1993).
Figure 6.
Carlos Chagas lecturing to doctors about Chagas’ disease. (Photo from Renato Clark Bacellar, Brazil’s Contribution to Tropical Medicine and Malaria, Rio de Janeiro, 1963)
The pathology of Chagas’ disease varies from a mild and inapparent infection as was found in Bernice, who outlived Carlos Chagas by twenty-seven years, to Rita, the three-year-old girl who died from a virulent acute infection. Because its pathology varies so widely, the diagnosis of Chagas’ disease from symptoms is difficult.
Animal studies were needed by Chagas to claim that Trypanosoma cruzi was the pathogenetic agent causing the fever and heart diseases. Even though the parasite had been found in insects and in a human, evidence was still lacking that it created the observed symptoms. Chagas sent some barbeiros infected with Trypanosoma cruzi to Cruz in Rio. Cruz injected the bugs’ intestinal contents into three uninfected callithrix monkeys. When the monkeys started dying some days later, Cruz cabled Chagas to come to Rio to see the results.
The journey from Lassance was a grueling twenty-four-hour trip, with two train changes and long waits. Chagas and Cruz knew that this discovery would place them, the Institute Oswa
ldo Cruz, and Brazil in the forefront of tropical medicine throughout the world. Cruz met Chagas at the railroad station and took him directly to the laboratory, where the mammalian pathogenicity of the flagellate was confirmed.
Figure 7.
Parasitic cycle of T. cruzi. (See Appendix 1.)
Carlos Chagas and Oswaldo Cruz later proved that T. cruzi passes from Triatoma infestans through fecal matter when these bugs defecate near the bite site. T. cruzi then enters through the skin or bite site into the human’s blood and nerve cells. The parasitic cycle of this disease included T. cruzias the pathogenic agent, which was transmitted by triatomine insects through their fecal matter to mammalian hosts (animals and humans). People become infected with T. cruzi by indirect contamination through the fecal matter of vinchucas and by direct transmission through blood or cells at birth and in blood transfusions and organ transplants. Vinchucas are directly infected with T. cruzi through their ingestion of the blood of infected animals and humans. T. cruzi transforms and reproduces in the vector and the host, both being necessary for its survival (see Figure 7).
Progression of Chagas’ Disease
Carlos Chagas discovered the symptoms and progression of Chagas’ disease. Figure 8 illustrates how Chagas’ disease progresses, which is a complex and in part unresolved issue. Primary Chagas’ disease refers to the acute infection stage, which may not be clinically apparent, with about 25 percent of infected patients indicating it (see Appendix 9). If apparent, it is characterized by inflammation that may include fever, general malaise, swelling and soreness of the lymph nodes and spleen, and by Signo de Romaña, severe swelling around the eye. People die or suffer permanent damage during the acute phase; those who survive have classic chronic or tertiary Chagas’ disease.
The Kiss of Death Page 4