Page 1 of 9
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.
Page 2 of 9
183
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.
Page 3 of 9
184
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.
Page 4 of 9
185
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
TREATMENT WITH A NITRO DERIVATIVE DRUG DOES NOT CURE THE DISEASE
From 1975, as a Professor and Researcher at the University of Brasilia, the author continued
his studies on the origin of autoimmunity in Chagas disease. The question of the origin of
natural phenomena always requires approaches with new ideas, without similarities, and the
research methodologies are not anticipated. Therefore, further experiments are needed to
confirm autoimmunity as a mechanism of self-harm in Chagas disease. How to continue the line
of research? Settling doubts was essential for the continuation of studies. ln the researcher's
mind, the important thing was to investigate whether Chagas' disease was authentic
autoimmunity. Further investigation was needed, and the restless unconscious decided it was
necessary to direct the study to confirm or deny his new theory of autoimmunity. The idea was
to treat T. cruzi chronically infected rabbits with trypanocidal nitro-derivative to reduce the
parasite load. lf treatment decreases the parasite load, avoids Chagas' heart disease, and
improves the prognosis, autoimmunity would be denied. However, iftreatment of the infection
does not improve the prognosis of the disease, then autoimmunity would be confirmed.
These experiments used three-month-old white rabbits treated with the nitro-derivative
benznidazole used for human disease. Rabbits have an average lifespan of 6-7 years, and the
results were repeated in two experiments, each group with eight rabbits. The Young
researchers found that the infected rabbits treated with nitro-derivative trypanocidal
benznidazole lived less than two years and had heart lesions like those documented in the only
infected rabbits. He also found that chronically infected rabbits treated with nitro derivative
lived less time than infected and untreated rabbits. The healthy control rabbits lacked the
lesions and lived longer than the rabbits in the previous groups. Conclusion: nitro-derivative
treatment did not improve the prognosis of Chagas disease in rabbits.
TREATMENT WITH NITRO DERIVATIVES HAS A GENOTOXIC EFFECT
Treatment of T. cruzi chronically infected rabbits with the nitro-derivative trypanocide decreases
the parasite load but does not prolong life or improve the patient's health. The destructive
lesions of self-harm were identical in the groups of treated or untreated rabbits. The toxic
reactions of the drug, such as testes atrophy, cancer, and encephalopathy, explain the lower
survival of animals treated with the genotoxic drug. Publications on the experimental treatment
of Chagas disease have caused controversy. Without a new effective drug to eradicate T. cruzi
infection, the pharmaceutical company Roche La Hoffman discontinued the nitro derivative
benznidazole. ln summary, treating chronically infected rabbits with nitro derivative
aggravates the health of Chagas disease patients. New questions popped into the scientist's
mind: - Why does the treatment decrease the parasite load and the disease continue? Concern
about the origin of autoimmunity in Chagas disease persisted. Another question was
unavoidable: "Why does the treatment decrease the parasite load but not improve the
prognosis of the disease? A new hypothesis emerged: - lf the DNA of the parasite is retained in
the genome of the Chagas disease patient, is it possible to explain the evolution of chronic
Chagas disease?
THE GENETIC ORIGIN OF CHAGAS DISEASE IS THE INTEGRATION OF THE
MITOCHONDRIAL DNA OF T. CRUZI INTO THE HUMAN GENOME
The enthusiasm for the results that confirmed autoimmunity generated several publications
and was essential for increasing the robustness of the collective work with the help of young
undergraduate and graduate students and postdoctoral fellows. ln fact, the new questions
Page 5 of 9
186
Advances in Social Sciences Research Journal (ASSRJ) Vol. 11, Issue 5, May-2024
Services for Science and Education – United Kingdom
suggested the integration of DNA from the flagellated protist into the genome of vertebrate
animals. A new hypothesis suggested the pathogenesis of Chagas disease was associated with
the integration of T. cruzi DNA sequences into the host genome. The team of researchers at the
Multidisciplinary Laboratory for Research in Chagas Disease at the Faculty of Medicine of the
University of Brasilia received training to initiate molecular biology studies necessary to
answer the question with no known antecedent. To this end, the PADCT/MCT/CNPq Program
approved funding for courses on molecular biology techniques related to the possible transfer
of exogenous DNA from protozoa to the genome of the mammalian host, with emphasis on the
state-of-the-art scientific procedure. Scientists from the USA, the United Kingdom, France, and
Brazil taught classes, and the technologies were demonstrated on the laboratory benches.
Graduate students at the University of Brasília and other Brazilian universities learned by
experimenting.
State-of-the-art research has been achieved and research has advanced with studies on animal
models of Chagas disease and humans. The work on this item was published in the journal Cell
in 2004, i.e., 25 years after the hypothesis of the genetic exchange of T. cruzi with the
mammalian host. Perhaps the result shocked critics of the Cell article, and the publication was
glossed over a year later: was the gloss of the article due to the unexpected result? The team of
researchers reacted and carried out a series of experiments, confirmed the previous results,
and then published them in prestigious international journals.
CHAGAS HEART DISEASE IN BIRDS IN THE ABSENCE OF TRYPANOSOMA CRUZI.
Skeptics returned to the criticism and said that it could be contamination with T. cruzi DNA
during persistent infection. It is up to the scientist to overcome the obstacles of new knowledge.
To placate the criticism, it was necessary to investigate and document results forcefully and
satisfy defenders of the supposed truth of a rationalist, authoritarian narrative without an
experimental basis. The project's author took it upon himself to respond to the criticism with
new, reproducible experimental findings. Based on previous experience with studies in birds'
refractory to T. cruzi, a new question emerged: - "lf birds are refractory to T. cruzi, would it be
possible to infect the fertile egg before incubation"? The experiments showed that inoculation
of T. cruzi into the air bubble of the egg does not prevent embryonic development. However,
chicks that hatch from eggs inoculated with T. cruzi eradicate the infection (negative nuclear
DNA (nDNA) test but retain mitochondrial, kinetoplast DNA minicircle sequences (kDNA test)
in the genome. Occasionally, nature allows access to its secrets. Eventually, the scientist
answers the question of a skeptical critic: - lt has been found that chicks hatched from inoculated
eggs eliminate T cruzi but retain sequences of minicircles of kDNA in the genome and, in
adulthood, develop Chagas disease like that of humans. Finally, a close relationship was
confirmed between the integration of T. cruzi kDNA mini-circle sequences in the host genome
and polygenic modifications with the pathogenesis of Chagas disease. The criticism ceased.
SEXUAL TRANSMISSION OF TRYPANOSOMA CRUZI FROM MALES OR FEMALES TO
HEALTHY PARTNERS
The story goes back to 1967, during his medical residency in pathology, when the young
pathology apprentice did post-mortem studies of acute Chagas disease cases. ln the first case,
the theca cells of the ovaries were parasitized by T. cruzi. ln the second case, the goniablasts of
the seminiferous tubes were parasitized by T. cruzi, and clumps of trypomastigotes and
Page 6 of 9
187
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
amastigotes filled the lumen of seminiferous tubes. The partial findings were published in the
Gazeta Médica da Bahia, in 1970. Nothing more was done at that time without intellectual
encouragement and essential research technologies.
ln the state of Pará, in 2010, a clinical-epidemiological study of two acute cases suggested
possible transmission by Assaí juice contaminated with T. cruzi. The author noted a case in an
upper-middle-class family where only one woman acquired the infection. The second case was
a man in a family that lived on the 10th floor of the building. As usual, the people of those
families drank Assaí juice. A doubt arose, and the question arose: why had only one individual
in each family acquired T. cruzi infection? Moreover, how can we explain the possible
transmission of the infection in the absence of triatomine vectors in luxury residences? The
memory of 1967 brought back the images of the post-mortem study of children with life-cycle
forms of T. cruzi in the testes and ovaries. Those images sustained the doubt and the question in
the restless mind: "Can American Trypanosomiasis be transmitted sexually?"
The following year, she was a physician in the Chagas Disease Health Care Program in Pará. She
began her doctorate under the Author's supervision at the University of Brasilia. The graduate
student and her team of colleagues from the Multidisciplinary Laboratory in Chagas Disease,
University of Brasília, went to examine patients in families with acute cases of Chagas disease at
the Barros Barreto Hospital, Federal University of Pará. Members of four families (109 people)
donated blood, and 21 adults from these families donated semen. Blood cell DNA studies
confirmed 76% (83/109) of individuals with positive nDNA and kDNA tests for T. cruzi.
Eighteen subjects had only a kDNA-positive test. Eight people had all tested negative. The
nDNA-PCR test on sperm adults in the families was positive in 82.6% of the cases (18/21).
However, the specific tests for T. cruzi antibody were positive in 28.4% (31/109) cases.
The differences between the results of antibody and PCR-nDNA tests are explained by the
phenomenon of immune tolerance. This phenomenon occurs when a microorganism infects the
embryo before the immune system matures; infection of the embryo by T. cruzi without the
specific antibody means acquisition through sexual life. Findings from the experiment in
humans and mice confirmed the sexual transmission of T. cruzi. The information was published
in the Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, in 2017, in the Journal of Visualized
Experiments, and the International Journal of Infectious Diseases, in 2019. Publications show the
leap in knowledge with the discovery of sexual transmission of Trypanosoma cruzi. The
scientists concluded that Chagas disease runs in families. This leap in knowledge calls for the
need for a robust program of Education, lnformation and Communication for Health, aiming at
the prevention and control of Chagas Disease.
MULTIDRUG TREATMENTOF CHAGAS DISEASE
Leaps in knowledge resulted from investigations initiated with new questions that generated a
hypothesis and demonstration of the genetically driven autoimmune pathogenesis of Chagas
disease. The advancement of knowledge led scientists to investigate the possibility of multidrug
treatment of Chagas disease and prevention of heart damage associated with mutations in
several genes. Experiments in the mouse model showed that the nitro derivative benznidazole
associated with azidothymidine (AZT) and ofloxacin significantly decreased the frequency of
kDNA mutations in the host genome. Groups of mice were infected with T. cruzi and treated with
benznidazole +AZT + ofloxacin. ln these experiments, one week after infection, the
Page 7 of 9
188
Advances in Social Sciences Research Journal (ASSRJ) Vol. 11, Issue 5, May-2024
Services for Science and Education – United Kingdom
mice were treated with all three drugs and sacrificed 250 days later. The tissues were subjected
to DNA extraction. PCR tests for kDNA amplification showed that treatment with benznidazole
+ AZT + ofloxacin decreased the number of mutations inserted into the genome by 2.44 times.
Of greater interest, mice treated simultaneously with all three drugs had residual, minimal
inflammation in the heart. However, persistent infection produces new mutations, but the
results reveal that multidrug treatment of Chagas disease in humans eliminates kDNA
mutations and, therefore, multidrug treatment will be indicated when an effective drug is
produced to eradicate T. cruzi infection.
TREATMENTOF HEART FAILURE BY BONE MARROW TRANSPLANTATION
Additionally, transplantation of histocompatibility bone marrow stem cells from birds with
kDNA mutations in the genome prevented destructive autoimmune damage to the heart. The
experiments were conducted with congenic Prague birds with histocompatibility haplotypes
C4C4 or B12B12. The fertile eggs of these birds of Prague (donated by the Prague Academy of
Sciences) were inoculated with T. cruzi and the hatched chicks developed the heart disease
typical of Chagas disease. The kDNA mutations were mapped in the host genome. ln the test
experiment, the destruction of bone marrow lymphocyte progenitor cells with cytostatic
(mileran) and anti-folate (chlorambucil) drugs, inoculated intravenously, three days before the
transfer of bone marrow cells from syngeneic healthy birds to kDNA-positive birds of the same
haplotype. ln the control experiment, healthy birds treated with anti-folate and cytostatic
received lymphocytes from syngeneic healthy birds. The results showed that the mutated
(kDNA- positive) birds that had their bone marrow cells destroyed with anti-folate and
cytostatic drugs and replaced by histocompatibility healthy cells did not have heart disease.
However, kDNA-negative control birds that received transplantation of cells from kDNA- positive birds developed heart disease typical of Chagas disease. This finding suggests that bone
marrow transplantation may treat advanced human heart disease when an effective drug is
produced to eradicate the infection.
CONCLUSION
The scientific revolution has overcome previous obstacles and led to the development of new
knowledge. On those occasions, new paradigms are accepted after experiments by scientists
bring forth confirmation and further scientific development. An example of a jump in
knowledge was the discovery of Trypanosoma cruzi, its invertebrate and vertebrate hosts, and
a new human disease by Dr. Carlos Chagas at the beginning of the last Century at Manguinhos
lnstitute, Rio de Janeiro. The Magnificent Discovery requires repeat information to students and
young scientists all over the Educational Systems.
The demonstration of Autoimmunity in Chagas disease by a young scientist at Cornell Medical
College is a scientific breakthrough. The research team from the Chagas Disease
Multidisciplinary Research Laboratory, Faculty of Medicine, University of Brasília recognized
other leaps of knowledge. To find out the origin of the pathogenesis of Chagas disease, there
was a need to focus on teamwork with undergraduates, master students (MS), doctorates
(PhD), and post-doctorates and their names are found in the publications' authorships. Early in
1984, the Author (head scientist) had postulated that the persistent myocarditis in humans and
animal models subjected to treatment with nitro derivatives (benznidazole or nifurtimox) could
Page 8 of 9
189
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
stem from integrating T. cruzi DNA into the host's genome. The investigation results showed
that the integration of mitochondrial sequences of minicircles (kDNA) from T. cruzi explained
the origin of the autoimmune Chagas myocardiopathy. The flagellate protozoan-induced
mutation in transposable elements of the human genome brings in polygenic alterations and
multifaceted manifestations of Chagas disease. The breakthroughs led scientists to investigate
possible multidrug treatment of Chagas disease to prevent mutation-associated heart pathology.
Additionally, the transplantation of healthy bone marrow cells into kDNA-mutated chickens
prevented the autoimmunity and heart destruction. At last, teamwork produced science led to
the discovery that the family-based silent Chagas disease is sexually transmitted. This late
breakthrough calls out the need for a strong Program of Education, lnformation, and
Communication for Health and Chagas disease control.
References
1. Kropf SKP. Chagas Disease, Brazil Disease. Fiocruz Publishing House, 2009.
2. Teixeira A. Chagas disease: a science fiction, Editora Kiron, 2017.
3. Chagas C. New human trypanosomiasis: Studies on the morphology and life cycle of Schizotrypanum cruzi n,
gen. Sp. Etiological agent of a new morbid entity in man. Memórias do lnstituto Oswaldo Cruz, 1(2): 159-218,
1911.
4. Chagas C. New morbid entity of man: general summary of an etiological and clinical study. Memórias do
lnstituto Oswaldo Cruz.3(2): 219-275, 1911.
5. Chagas C. American Trypanosomiasis. Acute form of molesty. Memories of the Oswaldo Cruz lnstitute, 8:37-
45, 1916.
6. Laranja C, Dias E, Nobrega G, Miranda A. Chagas Disease: A Clinical, Epidemiologic, and Pathologic Study.
Circulation, 1.035-1060, 1956.
7. -Buch CA, Teixeira ARL, Santos. The immunology of experimental Chagas disease lll: Rejection of allogenic
heart cells in vitro. Journal of Experimental Medicine, 140: 38-53, 1974.
8. Teixeira ARL, Roters F, Mott KE. Acute Chagas disease. Gazeta Médica da Bahia, 3: 170-86, 1970.
9. Teixeira ARL, Calixto MA, Teixeira ML. Chagas disease: carcinogenic activity of the antitrypanosoma
nitroarene in mice. Mutation Research, 305: 189-196, 1994.
10. Teixeira ARL, Córdoba, JC, Souto-Maior l, Solorzano E. Chagas disease: lymphoma growth in rabbits treated
with benznidazole. American Journal of Tropical Medicine Hygiene, 43: 146-158, 1990.
11. Teixeira ARL, Silva R, Cunha-Neto E, Santana JM, Rizzo LV. Malignant non- Hodgking's lymphoma in
Trypanosoma cruzi -infected rabbits treated with nitroarene. Journal of Comparative Pathology, 103: 37-48,
1990.
12. Lauria-Pires L, Braga MS, Vexenat AC, Nitz N, Simões-Barbosa A, Tinoco DL, Teixeira ARL. Progressive
chronic Chagas heart disease ten years after treatment with anti-Trypanosoma cruzi nitro derivatives.
American Journal of Tropical Medicine and Hygiene, 63(3-4): 111-8, 2000.
13. Morillo CA, Marin-Neto J A, Avezum A, Sosa-Estani S, Rassi JR. A Randomized Trial of Benznidazole for
Chronic Chagas Cardiomyopathy. New England Journal Medicine, 373: 1295-1306. 2015.
14. Nitz N, Gomes C, Rosa AC, D'Sousa-Ault M, Moreno F, Lauria-Pires L, Nascimento R J, Teixeira ARL. Heritable
Page 9 of 9
190
Advances in Social Sciences Research Journal (ASSRJ) Vol. 11, Issue 5, May-2024
Services for Science and Education – United Kingdom
integration of kDNA minicircle sequences from Trypanosoma cruzi into the avian genome. lnsights into
human Chagas disease. Cell, 118: 175-186, 2004.
15. Hecht MH, Nitz N, Araujo PF, Sousa AO, Rosa AC, Gomes C, Leonardecz E, Teixeira ARL. lnheritance of DNA
Transferred from American Trypanosomes to Human Hosts. PLoS ONE, r (2): e9181, 2010.
16. Teixeira ARL, Gomes C, Nitz N, Sousa A O, Alves RM, Guimaro MC, Cordeiro C, Bernal FM, Rosa AC, Hejnar J,
Leonardecz E, Hecht MM. Trypanosoma cruzi in the chicken model: Chagas-like heart disease in the absence
of parasitism. PLoS Neglected Tropical Diseases. 29; 5(3): e1000. 2011.
17. Teixeira AR, Nitz N, Bernal FM, Hecht MM. Parasite-induced genetically driven autoimmune Chagas heart
disease in the chicken model. Journal Visualized. Experiments. 29:3716. Doi: 10.3791/3716. 2012.
18. Araujo PF, Almeida AB, Pimentel CF, Silva AR, Sousa A, Valente AS. Teixeira ARL. Sexual transmission of
American trypanosomiasis in humans: a new potential pandemic route for Chagas parasites. Memórias
lnstituto Oswaldo Cruz, Rio de Janeiro, 112 (6): 437-446, 2017.
19. Almeida AB, Araujo FP, Rosa AC, Valente AS, ARL. Sexual transmission of American trypanosomes from males
and females to naive mates. Journal of Visualized Experiments, 2019.
20. Gomes C, Almeida AB, Rosa AC, Araujo PF, Teixeira ARL. American trypanosomiasis and Chagas disease:
Sexual transmission. International Journal of Infectious Diseases, 2019.
21. Teixeira ARL, Gomes CC, Sá A, Nascimento RJ, Lauria-pires L, Castro AM, Bernal FEM, Sousa AO. Trypanosoma
cruzi kDNA minicircle sequences integration into the host genome: a biomarker for monitoring the efficacy
of multidrug treatment of Chagas disease. International Journal Scientific Research Updates. 05(01) 170-207,
2023.
22. Guimaro MC, Alves RM, Rose E, Sousa AO, Rosa AC, Hecht MM, Sousa MV, Andrade RR, Vital T, Plachy J, Nitz
N, Hejnar J, Gomes CC, Teixeira ARL. lnhibition of Autoimmune Chagas-Like Heart Disease by Bone Marrow
Transplantation. PLoS Neglected Tropical Diseases, 8/12: e3384. 2014.