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International Centennial Symposium on the Discovery of Chagas Disease Rio de Janeiro July – 2009 Paulo Gadelha.

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Presentation on theme: "International Centennial Symposium on the Discovery of Chagas Disease Rio de Janeiro July – 2009 Paulo Gadelha."— Presentation transcript:

1 International Centennial Symposium on the Discovery of Chagas Disease Rio de Janeiro July – 2009 Paulo Gadelha

2 Cover of the book "My Father" / Watercolor by Glauco Rodrigues– 1993, Casa de Oswaldo Cruz - Fiocruz

3 Carlos Chagas (1878-1934) 1878 Born in Oliveira, in the state of Minas Gerais 1903 Graduated from the Medical School of Rio de Janeiro with a thesis on Malaria associated with the Manguinhos Institute 1904 Hired as Physician, General Directorship of Public Health 1905 Comissioned by Oswaldo Cruz to conduct a Malaria Campaign for the Hydroelectric Power Plant in Itatinga, SP. Advocates the Intra Domicile mosquito control strategy COC archives Fazenda Bom Retiro – Oliveira (MG)

4 1907 Goes to Lassance to fight a Malaria epidemic that halted the work of Central do Brazil Railway 1910 Member of the National Academy of Medicine 1912 Schaudinn Prize of Protozoology awarded by The Hamburg Institute of Tropical Medicine 1913 and 1921 indicated for the Nobel Prize 1917 Appointed Director of The Oswaldo Cruz Institute 1918 Coordinates the Brazilian Campaign to Fight the Influenza Pandemic 1919 Director of the National Department of Public Health 1921 Receives Doctor honorary degree, Harvard University 1925 Head of the Chair of Tropical Medicine, Medical School of Rio de Janeiro 1925 Member of the Hygiene Commission of the League of the Nations COC archives

5 “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, energy- laden, 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

6 Carlos Chagas' parents-Mariana Candida and Jose Justinario The author Carlos Chagas Filho at four years of age with his father COC archives

7 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

8 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

9 The Triad of Assistance, Research, and Education Public Health Models 1918 Led the campaign against Spanish Influenza 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 1928 Professorship of Tropical Medicine at Medical School 1925 First specialized course in Public Health Hygiene

10 Rural Prophylaxis Acervo COC

11 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. Founding of the Anna Nery School COC archives

12 Tropical Disease Pavilion at Sao Francisco Assis Hospital Technical-Scientific Council at the Rio de Janeiro School of Medicine-1933 Professor May 23, 1925 COC archives School of Medicine

13 " The more controversies we articulate, the vaster the world becomes”. " Bruno Latour, Joao Arriscado Nunes, Ricardo Roque. Impure objects-Experiments in science studies”.

14 Film

15 Paleoepidemiology of Chagas Disease, Adauto JG Araújo, Paulo C Sabroza, Luiz Fernando R Ferreira da Silva Rupestrian paintings. Capivara Mountain National Park, Piaui Coprolite in the pelvic cavity of a partially mummifyed corpse.Peruacu Valley, MG (Natural History Museum, UFM) Chagas Disease before Carlos Chagas

16 “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

17 First labs in Manguinhos, circa 1904. COC archives. The plasmodium in the blood. Drawing by Carlos Chagas for his medical doctor thesis, 1903. Mosquito vector. Manson, 1903. Carlos Chagas Experimental Medicine Background

18 Chagas Malaria Campaigns 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.

19 Tropical Medicine in the Brazilian Tropics Patrick Manson and the Liverpool School of Tropical Medicine, 1899: The idea of tropical diseases is “a concept more convenient than accurate” (1897) Bacteriology – cosmopolitan influenced by climate or geography 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.

20 “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)

21 Science, Public Health and Nation Building European Modernization of Rio de Janeiro, The new Republic’s Capital 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

22 The Discovery of a New Human Trypanosomiasis Expanding Economic Frontiers and Collecting Material Train station, Central do Brasil railway, Lassance, Minas Gerais.. COC archives

23 An engineer focuses Chagas attention on a “Kissing Bug”, the “Barbeiro” - Vinchucas. Findings of a flagellate, wrongly assumed to be Trypanosoma minasense. Experimental infection on tamarin (sagüi) reveals a new species, named Trypanosma cruzi. The Discovery of a New Human Trypanosomiasis

24 The barbeiro Prints by Castro Silva,in Carlos Chagas, New human trypanosomiasis. Studies on the morphology and life cycle of Schizotrypanum cruzi n. gen., n. sp., etiological agent of a new morbid entity of man), Memórias do Instituto Oswaldo Cruz, 1(2): 159-218, Aug. 1909. Stages of Trypanosoma cruzi

25 On April 14, 1909, Chagas found the parasite in the blood of a feverish child “In a feverish, sick individual with severe anemia, edemas, and engorged ganglions, we found trypanosomes whose morphology is identical to that of Trypanosoma cruzi. In the absence of any other etiology for the observed morbid symptoms and, further, pursuant to previous experiments with animals, we deemed this to be a human trypanosomiasis, a disorder caused by Trypanosoma cruzi, whose transmitter is Conorrhinus sanguissuga.” Brasil Médico, Research Note

26 Carlos Chagas tending to young Rita, Lassance, early 1910s. For a long time, it was believed that the girl in this photograph was Berenice, the first identified case of the disease. In the background, the Central do Brasil train car that provided Chagas with both lodging and laboratory space in Lassance. COC archives

27 The Social Construction of a Scientific and Public Health Fact A unique pathway 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. 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.

28 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) Bocio was considered the disease’s distinctive markPatients from the state of Goiás, 1912. COC archives COC archives

29 The National Campaign for Rural Sanitation (1916-1920) - “Brazil is an immense hospital” “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” Miguel Pereira

30 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 Glory and Ordeal of Chagas’ discovery

31 Worldwide Recognition Brazilian Pavilion, International Congress of Hygiene and Demography, held in June 1911, in Dresden, Germany. Schaudinn Prize Diploma, bestowed on Carlos Chagas by the Hamburg Institute for Tropical Diseases in Hamburg, Germany, June 22, 1912. COC archives

32 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 Ordeal (1913- 1935)

33 A Twofold Translation 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” From a “Brazilian Disease” to an “American Trypanosomiasis” Clinical Tools for easy diagnostic The Romaña Signal (swelling around the eyes and face) XIX Regional Pathology Society of Argentina, 1935 Electrocardiogram

34 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

35 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

36 100 Years Later A Neglected Disease Americas - 12-13.000.000 infected individuals / ~ 200.000 new cases/year (2000), 700.00/year (1983) / 33.000 – 50.000 deaths/year Brazil – 4500 deaths/year (H.M., Brazil, 2005) 4th ranking cause of death in Brazil due to parasitic infectious diseases 30% of acute cases will evolve to cardiac or digestive chronic illness The efficacy of the two major drugs (nifurtmox and benznidazole) for treatment of the acute phase is questionable. No vaccine available New sceneries epidemiológicos: the Amazon, Spain, Switzerland, France, Japan, Australia, Canada, and the US. Increasing role of new ways of transmission: transfusion, vertical, oral

37 Challenges Social and environmental policies A sustainable system of epidemiological surveillance Development of diagnostic methods rapid, low-cost tests for identifying chronic cases in endemic areas; specific and rapid diagnosis for the acute phase. markers for evolution, prognostication and cure. Development of new pharmaceuticals and therapeutic strategies development of new drugs. 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

38 Fiocruz Actions Research Interaction between the parasite and host Ecoepidemiology and the urbanization of Chagas disease Fisiopathology, Immunopathology and immunoregulation of Chagas Disease The association between AIDS and Chagas disease Diagnostics Molecular diagnosis of Chagas disease-PCR Secure diagnostic methods for blood banks Treatment Regenerative medicine-stems cells-cardiopathic treatment First heart transplant in RJ in partnership with Tthe National Institute of Cardiology Experimental chemotherapy for treating Chagas disease Chagas cardiopathy: Selenium Project Partnership between Fiocruz and Genzyme-development of new drugs

39 Management and Research Integrated Program for Chagas Diseas (PIDC) thematic network. Reference services International reference for taxonomy of triatomines Internet Portal. PIDC thematic network Global network for the elimination of Chagas disease (Global Network for Chagas Elimination-GNChE) Archives and Documentation Carlos Chagas Archives~-Brazilian heritage registered in the Memory of the World Program (MOW) of UNESCO Fiocruz Actions

40 Systems for Innovation and Financing of Neglected Diseases The scale-up of global health funding doubled from 1990 to 2001 and then doubled again by 2007. Over $2.5 billion was spent on neglected disease R&D in 2007. 80% went to three diseases: HIV/AIDS (42.3%), malaria (18.3%) and tuberculosis (16.0%). Public (69.4%) and philanthropic (21.0%) funders provided around 90% The US Government (70.4%) and European governments and the European Commission (21.7%). 95% of total philanthropic spend by the Bill & Melinda Gates Foundation ( 84.0%) and the Wellcome Trust (11.1%) 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

41 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.


43 42.3% of global funding received for research and development $125.1 MILLION total spend for kinetoplastid diseases research and development KINETOPLASTID DISEASES

44 “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

45 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)

46 "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.

47 “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

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