Keywords:
Chagas disease - neuropathology - history
Palavras-chave:
Doença de Chagas - neuropatologia - história
This article describes the remarkable pioneering contribution of Gaspar Vianna to
the knowledge of the neuropathology of Chagas disease, as described in one of his
works, Contribuição para o estudo da anatomia patológica da Moléstia de Carlos Chagas
[1] (Contribution to the study of the pathological anatomy of Carlos Chagas disease),
published in 1911. Although recognized as one of the great names in Medicine and Science
in Brazil[2],[3],[4],[5],[6], little prominence has been given to his fundamental study on central nervous system
(CNS) involvement in the acute phase of Chagas disease.
GASPAR VIANNA - A SHORT BIOGRAPHY
Gaspar de Oliveira Vianna ([Figure 1]) was born on May 11, 1885, in the city of Belém do Pará[3]. In 1903, shortly before turning 18, he moved to Rio de Janeiro and enrolled in
the Faculty of Medicine. In 1907, still a student, Gaspar Vianna was assigned as an
assistant to Bruno Alvares da Silva Lobo (1884 – 1945), director of the Laboratório
Anátomo-Patológico of the Hospital Nacional de Alienados, working under the supervision
of psychiatrist Juliano Moreira (1873 – 1933), the hospital's director. After his
graduation from medical school in 1908, although asked by Juliano Moreira to continue
his work at the Laboratório Anátomo-Patológico, Gaspar Vianna chose to accept an invitation,
in 1909, from Oswaldo Cruz (1872 – 1917), to work in the pathologic anatomy sector
of the Instituto Oswaldo Cruz. In the period between 1909 and 1914, the tirelessly
hard-working scientist published 21 works, reporting notable findings in the areas
of protozoology, microbiology, pathologic anatomy, and chemotherapy[3]. Gaspar Vianna died on June 15, 1914, at the premature age of 29, as a result of
an acute tuberculosis infection acquired while performing an autopsy on an infected
patient.
Figure 1 Gaspar Vianna (1885-1914) at the Instituto Oswaldo Cruz. Reproduced from reference
2 with the permission of the editor of the Memórias do Instituto Oswaldo Cruz.
HISTOPATHOLOGY AND PATHOGENESIS OF CHAGASIC ENCEPHALITIS
Following the clinical description, in 1909[7], of the new human disease caused by Trypanosoma cruzi, Carlos Chagas (1879-1934) invited Gaspar Vianna to write a histopathologic description
of this new entity. Working hard and with dedication, Gaspar Vianna studied organ
specimens from 10 patients autopsied by Carlos Chagas, one of whom, a three-month-old
infant, was the first fatal case in the acute phase of the disease. His findings were
published in 1911[1]. Below is a summary of the description by Gaspar Vianna of the chagasic encephalitis
observed in the three-month-old infant.
Irregularly distributed inflammatory foci of leukocytic infiltration of variable size
were seen in all examined regions of the CNS. The parasite, round-shaped, and containing
a nucleus and a kinetoplast (amastigote form), was identified in variable numbers
in many of the inflammatory foci, sometimes distending the parasitized cell. Based
on the position of the parasitized cell in the nerve tissue, the structure of its
nucleus, and its relation to the other components of this tissue, the author concluded
that the parasitized cell was a neuroglial cell.
Parasite multiplication occurs by successive binary divisions of the amastigotes,
followed by transformation of these into trypomastigotes, still inside the parasitized
cell. With rupture of the parasitized cell membrane, the trypomastigotes are released
and become capable of invading other cells. It is upon rupture of the parasitized
cell membrane that the inflammatory reaction is observed, leading to progressive disappearance
of the parasite in these foci. Also found are cells containing a large number of parasites,
but with no inflammatory reaction surrounding them, a finding that, according to the
author, corresponds to the early phases of CNS involvement in Chagas disease ([Figure 2]).
Figure 2 A. Chagasic encephalitis. A neuroglial cell distended by numerous amastigotes (parasites
containing a nucleus and a kinetoplast). The nucleus of the parasitized cell is observable
amidst the parasites. A neuron can be seen in the upper part of the figure. Reproduced
from reference 1 with the permission of the editor of the Memórias do Instituto Oswaldo
Cruz. B. Chagasic encephalitis. Neuroglial cell distended by a few amastigotes and
numerous trypomastigotes (parasites containing a nucleus, a kinetoplast, and a flagellum).
The nucleus of the parasitized cell is observable in the lower right of the figure.
Reproduced from reference 1 with the permission of the editor of the Memórias do Instituto
Oswaldo Cruz.
Over 100 years have elapsed, but very little has been added to Gaspar Vianna's observations[8]. Chagasic encephalitis is characterized by multiple foci of microglia, macrophages,
and neutrophils arranged in a nodular pattern (“microglial nodes”). When examined
under an electron microscope, the amastigote nests are located within the cellular
bodies and astrocyte processes, indicating that these are the main target cells for
T. cruzi
[9] invasion and proliferation. The perivascular arrangement of the astrocyte processes
could facilitate invasion by the parasite.
The pathogenesis of CNS involvement, as described by Gaspar Vianna, was confirmed
by subsequent studies. It consists of an inflammatory reaction produced by rupture
of the membrane of the parasitized cells. Macrophages from the blood or activated
microglia, along with neutrophilic granulocytes, are the cells responsible for phagocytosis
and removal of the parasites. Kinetic studies of experimental T. cruzi infection in rats show that the greater number of microglial nodes occurs one week
after the finding of an increased number of amastigote nests, indicating that the
microglial nodes are a reaction to the rupture of the parasitized cells[9]. The inflammatory nodes tend to disappear as the acute phase ends.
The first case of chagasic encephalitis in a chronic chagasic patient with chronic
lymphocytic leukemia (reactivated acute form)[10] was described in 1969. Other cases in immunodeficient individuals were subsequently
reported, particularly after the emergence of AIDS in 1981, many of whom presented
with the tumoral form of the disease (brain chagoma). This form is characterized by multifocal necrotizing encephalitis, abundant amastigotes
within astrocytes, apart from isolated forms dispersed through the cerebral parenchyma,
microglial nodules, and exudates of macrophages, lymphocytes and plasma cells and,
to a lesser degree, neutrophilic granulocytes within the nerve tissue and perivascular
spaces[9].
These pathological changes can also be explained by the pathogenic mechanism proposed
by Gaspar Vianna in 1911. In immunocompetent individuals, a robust cellular and humoral
immune response controls parasite replication during the acute phase[11]. However, if for any reason the immune system fails, reactivation of the acute phase
may occur: the amastigotes will be able to reproduce, differentiate into bloodstream
trypomastigotes that are released upon rupture of the host cell membrane, and extensively
invade the neighboring cells, which may result in necrosis of the nerve tissue, producing
the brain chagoma.
Gaspar Vianna deserves prominence as a rare example of a scientist who, in a single
publication involving the study of a single patient, made such an important contribution
to the knowledge of new aspects of a new human disease that had been discovered only
two years earlier. Also remarkable is that his description of the intracellular life
cycle of T. cruzi, and the histopathology and pathogenesis of CNS involvement in T. cruzi infection remains accurate and up to date.
