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 Oswaldo 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).