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Advances in Social Sciences Research Journal – Vol. 11, No. 5

Publication Date: May 25, 2024

DOI:10.14738/assrj.115.16972.

Teixeira, A. R. L. (2024). Leaps of Knowledge. Advances in Social Sciences Research Journal, 11(5). 182-190.

Services for Science and Education – United Kingdom

Leaps ofKnowledge

Antonio R L Teixeira

Chagas Disease Multidisciplinary Research Laboratory,

Center for Advanced Studies, University of Brasília, Brazil

ABSTRACT

Chagas Disease is the main cause of heart failure in the Western Hemisphere.

Initially restricted to the American continent, the people's migration to the

Northern Hemisphere caused the disease to become present in the five continents.

A scientific revolution occurs when an important discovery removes an obstacle to

the serial production of new scientific knowledge of social interest. Such a

revolution creates a paradigm accepted after experimental analysis and verification

by scientists investigating the subject. An example of a leap in knowledge was the

discovery of the protozoan Trypanosoma cruzi, its invertebrate and vertebrate

hosts, an agent of a new human disease recognized by Dr. Carlos Chagas at the

beginning of the twentieth century. Certainly, the seminal work of Carlos Chagas

inseminates enthusiasm that is essential to disturb the minds of scientists who

produce leaps of knowledge about recondite aspects of Chagas disease at the

University of Brasilia.

INTRODUCTION

ln 1908, Oswaldo Cruz appointed the young doctor Carlos Chagas to care for malaria, which

worsened the health of the extension works of the Central Railroad near Lassance, MG. With his

disciple Belizário Pena, they attended to patients in a locomotive car. The generous clinician

listened to the poor people and wrote everything down. He had in his mind the diagnoses of

diseases known to his teachers.During the nights, perhaps, he recalled the episodes ofthe death

of his father, his little brother, his uncle, and a college classmate who suddenly fell into his arms.

Carlos Chagas and Belizário Pena spent the night in a hut infested with the triatomines' blood

hickeys. They captured those hickeys that harbored flagellated protozoa in their feces. Chagas

sent them to Master Oswaldo Cruz with a letter, asking him to inoculate the contents of the

insects' intestines in guinea pigs. At that time, the interest in that observation existed only in

the refined discernment of the 30-year-old. Dr. Chagas thought this flagellated microbe was one

stage of the life cycle and that it could find other stages in the human body. Intoxicated by

curiosity, he examined a cat's blood under a microscope and found the trypanosome. He was

then informed by Oswaldo Cruz about the finding of the parasite in the blood of marmosets

inoculated with feces of contaminated hickey insects.

Chagas intensified the search for the parasite in his patients' blood. On April 15, 1909, when

examining the blood of 2-year-old Berenice, he found the trypanosome like that of the cat's

blood. ln that region, sometime later, a child died, and the post-mortem study showed

amastigote forms of the parasite dividing into the cells of the body. Chagas concluded that the

protozoan was the agent ofthe disease that victimized the child and designated it Trypanosoma

cruzi.

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Teixeira, A. R. L. (2024). Leaps of Knowledge. Advances in Social Sciences Research Journal, 11(5). 182-190.

URL: http://dx.doi.org/10.14738/assrj.115.16972

However, Berenice and other patients with the protozoan in their blood survived the febrile

infection and led normal lives. Then, Carlos Chagas's creative imagination made a new

hypothesis: "Would the initial infection persist in the body, and could it cause disease many

years later?" Thinking about people's health, he asked, " What would be the importance of

chronic infections for human health?" Further investigation was necessary. Until then, the

chronic phase of the infection existed only in his imagination.

Among the typical pathologies of the region, Carlos Chagas recognized the heart's aggravations

and various problems in the digestive system. it was necessary to expand the clinical study to

patients with signs of heart disease who could have chronic infections. This investigation

required a lot of trust in the thinking existing in his restless mind and a lot of work over the

years in the face of the lack of instruments, techniques, and media for culture, growth, and

identification of the infectious agent. His thinking was renewed when he examined patients

complaining of weakness, palpitations, slow and irregular heartbeats, and inconstancy of the

rhythm of the artery of the pulse. Doctor Chagas put his ear to the patient's chest to appreciate

the ictus cordis impulse in the chest. After four years away from his family, Oswaldo Cruz

convinced him to return to the Manguinhos Institute in Rio de Janeiro in the company of Artur

Neiva and Belizário Pena. With their students, they identified patients with clinical symptoms

of acute infection and Trypanosoma cruzi in the blood, and the new morbid entity was given the

epithet Chagas Disease.

Doctor Carlos Chagas (1879 – 1934).

By 1936, he felt weak and strained in his legs and could not go to work. Dr. Chagas attended the

inauguration of the institute's Hospital, but it was impossible to visit his laboratory. He died a

few days later, and the possibility that he succumbed to the disease he discovered cannot be

ruled out.

For decades, Chagas disease was discredited. However, a group of followers of Doctor Carlos'

work continued the study of patients with disease symptoms. Focusing on the clinical- electrocardiographic analysis of 180 cases of acute infection, 657 cases of asymptomatic

chronic infection, and 683 cases of heart disease, the researchers at the Manguinhos Institute

characterized chronic heart disease. The histopathological study documented T. cruzi in the

myocardium in 11 acute cases and 21 cases of chronic Chagas disease. The seminal work of the

scientists brought Chagas Disease, discovered, and recognized in Brazil, back to the Public

Health scene and was published in the journal Circulation in 1956.

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Advances in Social Sciences Research Journal (ASSRJ) Vol. 11, Issue 5, May-2024

Services for Science and Education – United Kingdom

NEWPARADIGM: AUTOIMMUNITY IN CHAGAS DISEASE

Scientists, physicians, and pathologists believed that Trypanosoma cruzi produced Chagas

disease by invading and destroying the tissues where it multiplied in the human body's cells.

The studies showed the protozoan in the heart in the early acute phase of infection. However,

the histopathological examination of chronic disease showed nests of T. cruzi in the heart in

about 10% of the deaths. Only in these cases was it possible to confirm the diagnosis of chronic

Chagas disease.

ln 1967, while doing his internship in pathology at the Hospital of the Federal University of

Bahia,the author performed a post-mortem study of a patient who died of chronic Chagas' heart

disease. The young pathology student examined that large, flaccid heart and the microscopic

study showed chronic myocarditis, with lysis of the heart fibers by the cells of the immune

defense system. For weeks, he examined slides with sections of the heart and finally found a

nest with amastigote forms of T. cruzi away from the lesion.

A question arose and remained in the mind of the young pathologist: "If the parasite destroys

the heart, why is it not found at the site of the injury?" After listening to the experienced masters,

he learned that it was very rare to find the parasite in the hearts of chronic patients. The doubt

remained in the apprentice's mind, and soon he thought: "lf the heart is not destroyed by the

mechanical action of T. cruzi, then those cells of the defense system do the destruction that

leads to heart failure"? From then on, he searched the scientific literature on autoimmune

diseases that produce pathology without an infectious agent. He established in his mind the

idea that the lesions in the heart were produced by the immune cells of the defense system.

With a restless mind, he wrote a project entitled "Autoimmunity in Chagas disease".

Upon completing his medical residency in Bahia, and with the certificate of approval from the

"Educational Council for Foreign Medical Graduates," the project's author was selected to

continue his studies in the pathology department of Cornell University Medical College in New

York. The work routine took up only half of his time in pathology. He presented his project to

theHead ofthe Department, telling him that he could perform the work of pathological anatomy

and investigate the idea explained in the project. The Boss read the project, smiled, raised an

eyebrow, and said: "Okay, but the methodology is missing"! He replied: "Yes, l am thinking of

learning cell culture to grow T. cruzi that l will use to infect rabbits".

ln the Cornell lab, the rabbits were infected and did not have acute febrile illness. All survived.

After two years, they began to die from the chronic disease. Histopathological studies showed

the destruction of the heart by the cells of the defense system in the absence of the parasite.

These findings supported curiosity and a new question: "lf it is the immune defense cells that

destroy the heart, prove that the cells (lymphocytes) of the infected rabbit destroy the normal

heart muscle cell. Healthy rabbit fetus heart cells were cultured in vitro and incubated with

lymphocytes from chronically infected rabbits and healthy control rabbits. Experiments have

shown that the lymphocytes of T. cruzi chronically infected rabbits destroy homologous healthy

heart fibers. These in vitro findings, combined with those in vivo in chronically infected rabbits,

confirmed the hypothesis that autoimmunity is the destructive mechanism of heart disease. The

study published in the Journal of Experimental Medicine in 1974 greatly impacted and affected.