Transcript Slide 1

International Centennial
Symposium on the Discovery
of Chagas Disease
Rio de Janeiro
July – 2009
Paulo Gadelha
Cover of the book "My Father" /
Watercolor by Glauco Rodrigues–
1993,
Casa de Oswaldo Cruz - Fiocruz
Carlos Chagas (1878-1934)
•
1878 Born in Oliveira, in the state of Minas
Gerais
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1903 Graduated from the Medical School of
Rio de Janeiro with a thesis on Malaria
associated with the Manguinhos Institute
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1904 Hired as Physician, General
Directorship of Public Health
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1905 Comissioned by Oswaldo Cruz to
conduct a Malaria Campaign for the
Hydroelectric Power Plant in Itatinga, SP .
Advocates the Intra Domicile mosquito
Fazenda Bom Retiro – Oliveira (MG)
control strategy
COC archives
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1907 Goes to Lassance to fight a Malaria epidemic that halted the
work of Central do Brazil Railway
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1910 Member of the National Academy of Medicine
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1912 Schaudinn Prize of Protozoology awarded by The Hamburg
Institute of Tropical Medicine
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1913 and 1921 indicated for the Nobel Prize
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1917 Appointed Director of The Oswaldo Cruz Institute
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1918 Coordinates the Brazilian Campaign to Fight the Influenza
Pandemic
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1919 Director of the National Department of Public Health
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1921 Receives Doctor honorary degree, Harvard University
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1925 Head of the Chair of Tropical Medicine, Medical School of
Rio de Janeiro
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1925 Member of the Hygiene Commission of the League of the
Nations
COC archives
“Let me isolate myself a little in the optimism of life
to redeem myself in your benevolent
incumbency. The charms of a tropical morning,
in which the suns spreads its biting, energyladen, rays over the earth, whose emerald-like
natural green is shinier than a Venetian crystal,
where universal harmony lives with man in a
more delicate sense, bringing deeper thought,
when the intense illumination of friendship
occurs, the pleasure of a thousand good
fortunes,affectionately dreamed (fragment).
Fragment of a letter from Carlos Chagas to his mother
COC archives
Carlos Chagas' parents-Mariana
Candida and Jose Justinario
The author Carlos Chagas Filho at
four years of age with his father
COC archives
Carlos Chagas at Manginhos on the veranda of the
Castle: Evandro (left) and Carlos (right) .Photo J.
Pinto
Iris Lobo Chagas and sons Evandro and Carlos .
COC archives
Rio Pardo Ranch in Avare, Sao Paulo. Carlos
Chagas with his hunting buddies.
.... accept your name as an Honorary Member of this
club, with unanimous and sincere applause..(from a
letter from the Botafogo Futebol Clube to Carlos
Chagas). April 23, 1919..
COC archives
The Triad of Assistance, Research, and
Education
Public Health Models
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1918 Led the campaign against Spanish Influenza
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1920 DNSP (National Department of Public Health) nationalized the
States' presence; sanitation code; amplification of pathologies treated(
tuberculosis, venereal Disease, and worker health); Ana Nery Nursing
School; Sao Francisco Assis Model Hospital; cooperation with
Rockefeller Foundation.
Education
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1928 Professorship of Tropical Medicine at Medical School
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1925 First specialized course in Public Health Hygiene
Rural Prophylaxis
Acervo COC
Founding of the Anna Nery School
Formal ceremony in homage to Ethel Parsons of
the Rockefeller Foundation, responsible for the
coordination of Sanitary Nursing. Rio de Janeiro,
July 1926.
Carlos Chagas surrounded by visiting nurses in July
1926.
COC archives
School of Medicine
Technical-Scientific Council
at the Rio de Janeiro School
of Medicine-1933
Professor May 23, 1925
Tropical Disease Pavilion at Sao
Francisco Assis Hospital
COC archives
" The more controversies we articulate, the
vaster the world becomes”.
" Bruno Latour, Joao Arriscado Nunes, Ricardo Roque.
Impure objects-Experiments in science studies”.
Chagas Disease before Carlos
Chagas
Coprolite in the pelvic cavity of a partially
mummifyed corpse.Peruacu Valley, MG
(Natural History Museum, UFM)
Rupestrian paintings.
Capivara Mountain National Park,
Piaui
Paleoepidemiology of Chagas Disease, Adauto JG Araújo,
Paulo C Sabroza, Luiz Fernando R Ferreira da Silva
Chagas Disease before Carlos Chagas
“At night I experienced an attack (for it deserves no less a name) of benchuca...the
great black bug of the pampas. It is most disgusting to feel the soft wing-less
insects, about an inch long, crawling over one’s body. Before sucking they are
quite thin but afterwards they become round and bloated with blood, and in this
state are easily crushed. One which I caught…was very empty. When placed on
a table, and though surrounded by people, if a finger was presented, the bold
insect would immediately protrude its sucker, make a charge, and if allowed,
draw blood. No pain was caused by the wound. It was curious to watch its body
during the act of sucking, as in less than ten minutes it changed from being as
thin as a wafer to a globular form.
Charles Darwin, Traveling Journals
Cited by Peter Hotez
Carlos Chagas Experimental Medicine
Background
The plasmodium in the blood. Drawing by Carlos Chagas for his
medical doctor thesis, 1903.
Mosquito vector.
Manson, 1903.
First labs in Manguinhos, circa 1904.
COC archives.
Chagas Malaria Campaigns
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•
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1905 Itatinga (SP), Santos Harbor Company
1907 Xerem (RJ), Office for Public Works
1907 Lassance (MG), EFCB
Hydroelectric power plant construction,Itatinga (SP).
Paula Machado Family archives.
Carlos Chagas in front of the Central do Brazil
Railroad Station. Lassance, 1908.
COC archives.
Tropical Medicine in the Brazilian
Tropics
Patrick Manson and the Liverpool School of Tropical Medicine, 1899:
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The idea of tropical diseases is “a concept more convenient than
accurate” (1897)
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Bacteriology – cosmopolitan influenced by climate or geography
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Tropical diseases – especially protozoology and helminthology –
vectors and hosts specific of tropical climates
Tropical Medicine in Brazil
Brings together lab microbiology with entomological field research based on
the classificatory mode of naturalists, and a more holistic environmental
approach.
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“The European nations, zealous of their colonies in the tropics, created in the
universities or in major research institutes a specialization: the study and
teaching of the pathology of warm climates. Here […] duties of the most
exalted and provident nationalism demand us to forcefully study and research
Brazilian nosology with the purpose of promoting the improvement of our
nation, of rare native traits, and to achieve, by prophylactic methods, the
sanitary redemption of our vast territory”
(Carlos Chagas, inaugural lecture as the Chair of Tropical Medicine, FMRJ, 1926)
Science, Public Health and Nation
Building
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European Modernization of Rio de Janeiro, The new Republic’s Capital
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Rethinking the Nation: The integration of the hinterland (“Sertões”).
“Manguinhos , in its few years of existence […] has done
more for the country than a whole century of rhetorical
[baccalaureate] omnipotence. The salvation is there”
Monteiro Lobato, 1918
The Discovery of a New Human
Trypanosomiasis
Expanding Economic Frontiers and Collecting Material
Train station, Central do Brasil railway,
Lassance, Minas Gerais.
.
COC archives
The Discovery of a New Human
Trypanosomiasis
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An engineer focuses Chagas attention on a “Kissing Bug”, the “Barbeiro” Vinchucas.
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Findings of a flagellate, wrongly assumed to be Trypanosoma minasense.
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Experimental infection on tamarin (sagüi) reveals a new species, named
Trypanosma cruzi.
The Social Construction of a Scientific and Public
Health Fact
A unique pathway
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Started with the identification of a vector, the etiological agent and major
features of its epidemiology, and proceeded with the effort of identifying an
associated disease, with no prior clinical evidence to support this theory.
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From the early stages, even without convincing etiological and
epidemiological evidence - ten years after the discovery, only 40 cases were
indisputably ascertained by lab procedures - Chaga’s disease was claimed to
be a major public health problem and a strong hindrance to the countries
progress.
•
The proof of the existence of a new disease entity led to a cognitive and
social construction process that extended for over three decades.
The Sertaoes ( Hinterlands): The Hidden Nation
and the Degeneration of its Population.
The new trypanosomiasis “creates, in vast regions of Minas Gerais
and other Brazilan states, a population of degenerates, utterly
unfit for the progressive evolution of our country” (Chagas, 1911)
Patients from the state of Goiás, 1912. COC archives
Bocio was considered the disease’s distinctive mark
COC archives
The National Campaign for Rural
Sanitation (1916-1920) - “Brazil is an
immense hospital”
Miguel Pereira
“Poor pariahs, who dwell in the most sordid misery, in shelters of straw or adobe
bursting with pinchugas,beadbugs (percevejos) and fleas[…] This is the banal
picture of the pinchugas regions. Dr. Neiva and myself saw in the north of
Goiás infernal images that only the Florentine poet could describe, by creating
a new cycle to his famous inferno”
Glory and Ordeal of Chagas’
discovery
• Glory (1909-1913):
• Recognition of the excellency of Brazilian Science
• Consolidation of the Oswaldo Cruz Institute
• Banner to the Movement of Rural Hygiene
• Public Health role in Nation Building and Economic and Social
Development
• Chagas indicated for The Nobel Prize
Worldwide Recognition
Schaudinn Prize Diploma, bestowed
on Carlos Chagas by the Hamburg Institute
for Tropical Diseases in Hamburg, Germany,
June 22, 1912.
Brazilian Pavilion, International Congress of
Hygiene and Demography, held in June 1911,
in Dresden, Germany.
COC archives
Ordeal (1913- 1935)
• Questioning the clinical
characterization and the
epidemiological magnitude: rarity
rather than “national scourge”
• Political dimension: to preserve the
countries image
• The Tropical Medicine Program under
criticism
A Twofold Translation
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From Endemic Parasitic Thyroiditis (Goiter and Cretinism)
to a Chronic Chagas Cardiopathy and Nervous Disease
• Acute and Chronic disease
• The silent stage and “potentially cardiac patients”
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From a “Brazilian Disease” to an “American Trypanosomiasis”
Clinical Tools for easy diagnostic
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The Romaña Signal (swelling around the eyes and face) XIX Regional
Pathology Society of Argentina, 1935
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Electrocardiogram
At last, a Significant Prevalence
Revealed
• Brazilian Public Health Expeditions
• Identification of cases in Argentine by Salvador Mazza
• Emanuel Dias and The Bambui project: Center for the Study
and Prophylaxis of Chagas Disease (CEPMA), 1943
History of Decisive Actions for the Control
of Chagas Disease in Brazil
1943 Creation of a research center at the Oswaldo Cruz Institute in Bambui, Minas Gerais.
1948 Gammexane
1950 First health campaigns
1975 Institution of a program with national reach, with research into serum-prevalence in the
rural population, national entomological research and electrocardiography research.
1980 Complete coverage of the area considered endemic, synthetic pyrethroids.
1991 Creation of the Southern Cone Initiative (Incosur)
Systematized methodology.
1999 - Beginning of the certification process for triatome vectorial transmission interruption.
2001 – National survey of serum-prevelance for assessment of the impact of control actions
2006 – Certification of the interruption of vectorial transmission by T. infestans
2007 Global Network for the Elimination of Chagas Disease.
Clássicos da Doença de Chagas,
Fiocruz 2009
100 Years Later
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A Neglected Disease
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Americas - 12-13.000.000 infected individuals / ~ 200.000 new cases/year
(2000) , 700.00/year (1983) / 33.000 – 50.000 deaths/year
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Brazil – 4500 deaths/year (H.M., Brazil, 2005)
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4th ranking cause of death in Brazil due to parasitic infectious diseases
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30% of acute cases will evolve to cardiac or digestive chronic illness
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The efficacy of the two major drugs (nifurtmox and benznidazole) for
treatment of the acute phase is questionable.
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No vaccine available
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New sceneries epidemiológicos: the Amazon, Spain, Switzerland, France,
Japan, Australia, Canada, and the US.
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Increasing role of new ways of transmission: transfusion, vertical, oral
Challenges
Social and environmental policies
A sustainable system of epidemiological surveillance
Development of diagnostic methods
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rapid, low-cost tests for identifying chronic cases in endemic areas;
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specific and rapid diagnosis for the acute phase.
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markers for evolution, prognostication and cure.
Development of new pharmaceuticals and therapeutic strategies
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development of new drugs.
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therapeutic experiments using combinations of existing drugs.
Keep vectorial transmission under control
Increase international control of blood banks
Accessibility of the infected to diagnosis and treatment
Development of new immunological and cellular therapies
Fiocruz Actions
Research
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Interaction between the parasite and host
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Ecoepidemiology and the urbanization of Chagas disease
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Fisiopathology, Immunopathology and immunoregulation of Chagas Disease
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The association between AIDS and Chagas disease
Diagnostics
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Molecular diagnosis of Chagas disease-PCR
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Secure diagnostic methods for blood banks
Treatment
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Regenerative medicine-stems cells-cardiopathic treatment
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First heart transplant in RJ in partnership with Tthe National Institute of Cardiology
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Experimental chemotherapy for treating Chagas disease
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Chagas cardiopathy: Selenium Project
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Partnership between Fiocruz and Genzyme-development of new drugs
Fiocruz Actions
Management and Research
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Integrated Program for Chagas Diseas (PIDC) thematic network.
Reference services
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International reference for taxonomy of triatomines
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Internet Portal. PIDC thematic network
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Global network for the elimination of Chagas disease (Global Network
for Chagas Elimination-GNChE)
Archives and Documentation
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Carlos Chagas Archives~-Brazilian heritage registered in the Memory
of the World Program (MOW) of UNESCO
Systems for Innovation and Financing
of Neglected Diseases
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The scale-up of global health funding doubled from 1990 to 2001 and
then doubled again by 2007.
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Over $2.5 billion was spent on neglected disease R&D in 2007.
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80% went to three diseases: HIV/AIDS (42.3%), malaria (18.3%) and
tuberculosis (16.0%).
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Public (69.4%) and philanthropic (21.0%) funders provided around
90%
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The US Government (70.4%) and European governments and the
European Commission (21.7%).
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95% of total philanthropic spend by the Bill & Melinda Gates
Foundation ( 84.0%) and the Wellcome Trust (11.1%)
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The private sector contributed 9.1% ($231.9 million) of global funding,
making this group the third largest source of investment after the NIH
and the Bill & Melinda Gates Foundation.
G-FINDER - survey of global investment into
R&D of new products for neglected diseases - 2007
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UN reform, consolidated in 1995, changed profoundly the
logic of governance, financing, and technical cooperation,
looking to reduce the role of multilateralism.
•
The agenda of the givers became more important than that
of the receivers, removing the regulatory role of WHO,
seeing it as merely the administration of funds and fostering
technical cooperation and project focus.
KINETOPLASTID DISEASES
42.3%
of global funding received for
research and development
$125.1 MILLION
total spend for kinetoplastid
diseases research and
development
Leishmaniasis
Sleeping
Sickness
Chagas
Disease
Multiple
kinetoplastids
Total
x
16,961,019 21,890,911
2,560,030
16,710,088 20,535,164
1,255,000
5,875,634
1,301,235
x
5,116,265
972,031
3,165,251 19,218,944
42,711,992 62,617,049
No reported funding in this category
Category not included in G-FINDER
6,222,783
ed
3,581,215
%
To
ta
l
ec
ifi
ns
p
U
Ve
c
co tor
n
pr tro
od l
uc
ts
s
os
tic
gn
ia
D
Va
(th cci
er ne
ap s
eu
tic
)
Va
(P cci
re ne
ve s
nt
iv
e)
gs
ru
D
B
a
re sic
se
ar
ch
Table 6. Funding for kinetoplastids product R&D in 2007 (US$)
54,664
51,270,622
41.0
2,811,906
56,543
x
41,368,700
33.1
x
922,522
377,918
649,983
10,099,322
8,1
x
6,222,783
x
7,315,643
x
434,460
x
704,647
22,384,194
125,122,839
17,9
100
“We have the technology in hand to develop new antipoverty
drugs, vaccines, and diagnostics, but it is financial
innovation that is most needed in order to promote
institutions for conducting scale-up processs
development, manufacturing, and clinical testing and for
securing global access for these new products”
Peter Hotez , 2008
The greatest challenge: there are an
abundant ideas and players, what is lacking
is an organic system, an architecture.
“There is also considerable confusion about
how all these new entities fit together, as
well as how they mesh with old-timers
such as WHO, the UNICEF, and the
World Bank. “There´ve been lots of
creative ideas and lots of new people”,
says Barry Bloom, dean of Harvard
University School of Public Health. “ But
there´s one missing piece. There´s no
architecture of global health.”
(Science, January 13, 2006)
"for Chagas, only science directed towards the betterment
of humanity was valid (…) Thus he never forgot that
social and economic factors are responsible -to a very
great extent-for the situations he witnessed. In this way
he was a precursor to what is most noble about social
medicine. In this respect it is important to remember his
words about the elimination of American
Trypanosomiasis from our territory, that the construction
of decent housing, compatible with healthy way of life,
was the most necessary element."
Carlos Chagas Filho – Meu pai.
“It won't take long for us to pass along a
beautiful and strong science which creates
art in the support of life”
Carlos Chagas