Emerging Chagas Disease


by

Antonio Teixeira, Marina Vinaud, Ana Maria Castro

DOI: 10.2174/97816080504131090101
eISBN: 978-1-60805-041-3, 2009
ISBN: 978-1-60805-569-2



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The book focuses on a global problem challenging the health systems. Trypanosoma cruzi infections are transmitted by cone-nosed triato...[view complete introduction]

Table of Contents

Foreword

- Pp. i-ii (2)

Wanderley de Souza

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Preface

- Pp. iii-iv (2)

Antonio Teixeira

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Contributors

- Pp. v-vii (3)

Antonio Teixeira, Marina Vinaud and Ana Maria Castro

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History of Chagas Disease as a Public Health Problem in Latin America

- Pp. 1-9 (9)

João Carlos Pinto Dias and Christopher John Schofield

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Endemic Chagas Disease

- Pp. 10-17 (8)

Antonio Teixeira, Rubens Nascimento and Nancy R Sturm

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Chagas Disease: A Global Health Problem

- Pp. 18-23 (6)

Ana Maria Castro, Marina Clare Vinaud and Antonio Teixeira

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Triatomine-Vector of Trypanosoma cruzi Infection

- Pp. 24-39 (16)

Liléia Diotaiuti

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A Review on the Ultrastructure of Trypanosoma cruzi

- Pp. 40-62 (23)

Wanderley de Souza, Kildare Miranda, Narcisa Leal Cunha e Silva and Thaïs Souto-Padrón

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Trypanosoma cruzi Mitochondrial DNA and the Parasite Lifecycle

- Pp. 63-69 (7)

Nancy R. Sturm

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Trypanosoma cruzi Nuclear DNA and its Correlation with the Parasite Lifecycle

- Pp. 70-82 (13)

David A. Campbell

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Host-Parasite Biology of Trypanosoma cruzi Infection

- Pp. 83-93 (11)

Conrad L. Epting, Kevin M. Bonney, Cheryl L. Olson and David M. Engman

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Acquired Immunity against Trypanosoma cruzi Infection and Vaccine Development

- Pp. 94-103 (10)

Maurício Martins Rodrigues, Bruna Cunha de Alencar and José Ronnie Vasconcelos

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Clinic Presentation of Chagas Disease

- Pp. 104-109 (6)

Antonio R.L. Teixeira

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The Pathology of Chagas Disease

- Pp. 110-121 (12)

Antonio Teixeira, Fernando Pimentel and Ciro Cordeiro

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Lateral Transfer of Minicircle Sequences of kDNA from Trypanosoma cruzi to the Genome of the Vertebrate Host

- Pp. 122-131 (10)

Nadjar Nitz and Antonio Teixeira

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The Pathogenesis of Chagas Disease in Mammals and Birds

- Pp. 132-137 (6)

Antonio RL Teixeira, Nadjar Nitz, Perla F Araujo and Mariana M Hecht

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The Treatment of Chagas Disease

- Pp. 138-144 (7)

Liana Lauria-Pires, Ana de Cassia Rosa, Rozeneide Magalhães and Cleudson Nery de Castro

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Perspectives in Drug Development for Chagas Disease Therapy

- Pp. 145-155 (11)

Izabela M. Dourado Bastos, David Neves, Meire M. Lima and Jaime M. Santana

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Environment, Interactions Between Trypanosoma cruzi and its Host, and Health

- Pp. 156-167 (12)

Antonio Teixeira, Clever Gomes, Silene Lozzi, Mariana Hecht, Ana Rosa, Pedro Monteiro,, Ana Bussacos, Nadjar Nitz and Concepta McManus

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Medical-Social Aspects of Chagas Disease

- Pp. 168-173 (6)

Antonio Teixeira, Mariana Hecht and Alessandro Sousa

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Index

- Pp. 174-180 (7)

Antonio Teixeira, Marina Vinaud and Ana Maria Castro

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Foreword

In 2009 the Brazilian scientific community, especially those involved in biomedical sciences, are celebrating what has been considered, up to now, the most important contribution of Brazilian science: the description, in a seminal paper published by Carlos Chagas (Nova Tripanozomiase Humana: estudos sobre a morfolojia e o ciclo evolutivo do Schyzotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem. Mem. Inst. Oswaldo Cruz 1 (2): 159-218, 1909) of what we presently know as Trypanosoma cruzi and Chagas’ disease. In addition to the description of a new genus and a new species, initially designated as Schyzotrypanum cruzi, Chagas identified a new disease. Later on this disease was named Chagas’ disease or American Trypanosomiasis. Chagas showed that the protozoan was transmitted by insects of the Reduviidade family to man and other mammals and he established the basic data of the lifecycle of the protozoan. Nowadays, the contents of the original paper are still a source of inspiration for those working on this subject. Since the original description thousands of papers have been published dealing with T. cruzi and Chagas disease. From a balance of these papers we can see that some changes have taken place, even in the Portuguese language. Indeed, some words at the time written with the letter j (morfolojia, ajente, etiolojico) are now written with the letter g (morfologia, agente, etiológico). It has been shown that the process of intracellular division of T. cruzi is not a schizogonic process, which takes place in members of the Apicomplexa Phylum. Therefore, the protozoan does not belong to a new genus Schyzotrypanum but to the previously known genus Trypanosoma. However, in view of some peculiarities shared with other species such as T. dionisii, T. myoti and T. vespertilionis among others, we still use the word Schyzotrypanumas indicative of a sub-species Trypanosoma(Schyzotrypanum) cruzi.

Since the initial description of T. cruzi thousands of papers dealing with the protozoan itself and with the disease caused by it have been published by the Brazilian scientific community. In view of some characteristics of the parasite, including (a) its differentiation process, (b) the morphology of the kinetoplast and (c) the ability to infect most of the mammalian cells, T. cruzi is considered a classical biological model. Indeed, the modern Cell Biology, Biochemistry, Molecular Biology, Immunology and Pathology in Brazil grew using T. cruzi and Chagas disease as experimental models. It is important to point out that Brazilian agencies supporting scientific activity stimulated research in this area. Programs such as the Programa Integrado de Pesquisas em Doenças Endêmicas (PIDE) (Integrated Programme of Research on Endemic Diseases) played a major role on the advances of research activities in Brazil in Chagas’ disease area. Subsequently, the World Health Organization created a similar program (TDR). Taken together, the existence of these programs stimulated the Brazilian scientific community to work with T. cruzi and Chagas disease. This in part explains why Brazilian Parasitology now occupies the third position in the world when we consider the number of papers published in international journals, while in other areas of science we occupy the tenth or eleventh position.

During all these years intense research activity took place in Brazil. Specialized scientific meetings were organized, such as the Caxambu meeting, which was recognized as the most important one in this field, attracting colleagues from different countries to Brazil every year. Thanks to these efforts the Brazilian health authorities launched special programs to control the reproduction of the insects which transmit T. cruzi inside houses, mainly in the rural areas. As a result, the number of new cases of Chagas’ disease was drastically reduced. This important achievement led some authorities to believe that Chagas disease was no longer a health problem in Brazil. However, this is a complete misunderstanding of the dynamics of parasitic diseases caused by protozoa and transmitted by insects. In spite of the optimistic view of some health organizations and health authorities, caution must predominate in this case. It is important to remember that many parasitic diseases, including Chagas’ disease, are caused by protozoa which infect several insect species and with multiple animal reservoirs. Successful elimination of one species, as happened with Triatoma infestans, the main vector involved in Chagas’ disease transmission in Brazil, may lead to the occupation of vacant niches by other triatomine species. As an example, infected Panstrongylus megistus was recently found by Ana Jansen and co-workers inside residences of neighbors to the Primatology Center of Rio de Janeiro, located only 100 km from Rio de Janeiro city. In addition, 26.5% of the 198 non-human primates from 18 species of 8 genera housed at this Primatology Center are also infected. Another important example comes from the finding that 64% of the nonhuman primate Leontopithecus rosalai adults, known as the golden lion tamarins, captured in the Poço das Antas National Park, localized only 60 km from Rio de Janeiro, are infected with T. cruzi. The parasite found by Jansen and co-workers in the golden lion tamarins belongs to the type II lineage, which in Brazil is usually associated with human cases of Chagas’ disease. Since (a) National Parks are sites where animal life must be preserved; (b) T. cruzi circulates among vertebrate and invertebrate hosts living in such parks; (c) sylvatic species may adapt to an anthroponotic transmission, and reinvasion of insects from sylvatic transmission cycles is a problem to control Chagas’ disease; (d) contact between wildlife, domestic animals and humans is a consequence of the increase in habitat fragmentation, intensified hunting, ecotourism projects and management practices, we can conclude that it is almost impossible to eradicate the parasite. Taking into consideration that (a) there are no vaccines against T. cruzi; (b) there are no efficient drugs to kill the protozoan; (c) several basic questions about mechanisms of interaction of the parasite with the hosts have not yet been solved and (d) that this parasite is an important experimental model to study basic biological processes, including cell differentiation, parasite-vector interactions, RNA-editing, RNA-splicing, extranuclear DNA organization and function, among others. It would be a tremendous and serious mistake to reduce the priority and the funds available for research on Chagas’ disease based on the false assumption that the disease will be eradicated.

Thanks to the efforts of the Brazilian community research activity in T. cruzi biology and Chagas disease takes place in several laboratories in Brazil. This book, organized by Antonio Teixeira, covers all areas of research, from the structural organization of T. cruzi to the perspectives in drug development and therapy of Chagas disease. Certainly, this initiative is a hallmark of the commemoration of the centennial anniversary of the discovery of Trypanosoma cruzi and Chagas disease.

Wanderley de Souza
Federal University of Rio de Janeiro


Preface

Chagas Disease is the most lethal endemic infectious disease in the Western Hemisphere, having a devastating effect on Latin American populations. The World Health Organization (WHO) has estimated that 18 million people are infected with Trypanosoma cruzi, the causal agent of Chagas disease. In endemic regions, field studies show mortality rates due to Chagas disease may be as high as 0.56%, with approximately 100.000 people dying from the disease per year. Usually Chagas patients die when they are between 30 and 45 years of age. According to the WHO/World Bank Chagas disease is a major burden inflicting an economic loss of six billion dollars annually. Chagas disease emerged among the settlers after the triatomine insect-transmitter adapted to human domiciles, and its endemicity expanded exponentially in the XIX century.

The major Amazon Basin tropical rain forest ecosystem, which was in the past considered Chagas disease-free, where new settlements, and ecosystem predation provide fertile conditions for the insect-vector to attack the human population, is now under epidemiologic surveillance for curtailing micro-epidemics detected in various counties. Currently, Chagas disease is no longer restricted to the poor people in remote rural areas of South and Central America. Autochthonous cases of Chagas disease have been reported, occasionally, in the United States, where the zoonotic T. cruzi infections are widely spread below Parallel 42ºN. Chagas disease is among other neglected infectious disease, such as Hanseniasis, Tuberculosis, Leishmaniasis, and Onchocerchiasiss.

Yearly, transfusions of contaminated blood contributes with thousands of new Chagas disease cases, now affecting a very broad social spectrum. The rural exodus has now made Chagas disease cosmopolitan. The T. cruzi-infected individuals migrating to North America, Europe, Asia, Africa, and Oceania pose a major threat, and this disease is presently in various continents. A further mode of transmission, congenitally from mother to offspring, contributes to its increase. Chagas disease thus represents a public global health problem, and its curtailment requires international solidarity. Nevertheless, the investments required for its control and prevention have not been sufficient to minimize current levels of T. cruzi transmission to humans. The disease is considered incurable. The drugs available to treat the infection are unsatisfactory, and developing a preventive vaccine is proving to be a challenge, awaiting the specific scientific advancement. Chagas Disease prevention and control require further studies on the ecological conditions and environmental changes related to the complex epidemiological chain that links forty species of invertebrate transmitters of the protozoan parasite to over 1250 mammal species dwelling in various ecosystems throughout the American Continents.

This book presents and discusses the scientific achievements made since Dr. Carlos Chagas (1909) demonstrated the T. cruzi in the blood of a feverish child. In the following decades the endemic Chagas disease in Argentina was reported by Salvador Mazza. The multidisciplinary approaches used in the studies of Chagas disease, involving environmental sciences, zoology, epidemiology, parasitology, pathology, internal medicine, biochemistry and molecular biology, and genetics give the readers a balanced view about the role the scientific development have played in the prevention and control of the T. cruzi infections, and in the paliative treatment of the Chagas disease severe clinic manifestations.

In this book the reader will find update information on Chagas disease with its increasing economic toll. In addition to the public usually interested in neglected diseases, human and veterinarian hospital blood-bank health workers, world travelers, and policy-makers, the emergence of Chagas disease worldwide has become of great interest of the general public, particularly in the last five years, after the alert was given by Health Authorities in various countries, concerning its acquisition by blood transfusion and congenitally.

The Editors wish to thank hundreds of laboratory workers, colleagues who have carried out the scientific research reported in the chapters of this book. Their contributions are indicated in the text, legends of figures as well as in the references used in the reviews. Particularly, we acknowledge the financial support of the Funding Agencies all over the World, which made possible the impressive scientific development important to protect the people’s health. Specifically, the Brazilian Funding Agencies, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Financiadora de Estudos e Projetos (FINEP), Ministério de Ciência e Tecnologia (MCT), Brazil, The National Institutes of Health (NIH), USA, and public and private organizations that have funded the research of the Authors of this Book, are acknowledge.

I express my gratitude to all my colleagues who have contributed to this book.

Antonio Teixeira
University of Brasilia

List of Contributors

Editor(s):
Antonio Teixeira
University of Brasilia
Brazil


Marina Vinaud
Universidade Federal de Goiás
Brazil


Ana Maria Castro
Universidade Federal de Goiás
Brazil




Contributor(s):
João Carlos Pinto Dias M.D., Ph.D.
Senior Researcher, Centro de Pesquisas René Rachou
Instituto Oswaldo Cruz
Belo Horizonte
Brasil


Christopher John Schofield Ph.D.
Honorary Senior Lecturer, ECLAT Coordinator
London School of Tropical Medicine
UK


Antonio Teixeira M.D., Ph.D.
Professor, Chagas Disease Multidisciplinary Research Laboratory
Faculty of Medicine
University of Brasilia, Federal District
Brasilia, 70.910-900
Brazil


Rubens Nascimento Ph.D.
Researcher, Chagas Disease Multidisciplinary Research Laboratory
Federal District
Brasilia, 70.910-900
Brazil


Nancy R. Sturm Ph.D.
Associate Researcher, Department of Microbiology
Immunology & Molecular Genetics
University of California at Los Angeles
California, 90095-1489
USA


Ana Maria Castro Ph.D.
Associate Professor, Department of Microbiology
Immunology, Parasitology and Pathology
Tropical Pathology and Public Helath Institute , Universidade Federal de Goiás
Goiânia, 74.605-050
Brazil


Marina Claude Vinaud Ph.D.
Associate Professor, Department of Microbiology
Immunology, Parasitology and Pathology, Tropical Pathology and Public Helath Institute
Universidade Federal de Goiás
Goiânia, 74.605-050
Brazil


Lileia Diotaiuti M.D., Ph.D.
Senior Researcher, Centro de Pesquisas René Rachou
Instituto Oswaldo Cruz, Belo Horizonte
Brasil


Wanderley de Souza M.D., Ph.D.
Professor, Laboratório de Ultraestrutura Celular Hertha Meyer,
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro
CCS-Bloco G, Ilha do Fundão, Rio de Janeiro
Rio de Janeiro, 21941-900
Brasil


Kildare Miranda Ph.D.
Associate Professor, Laboratório de Ultraestrutura Celular Hertha Meyer,
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro
CCS-Bloco G, Ilha do Fundão, Rio de Janeiro
Rio de Janeiro, 21941-900
Brasil


Narcisa Leal Cunha e Silva Ph.D.
Associate Professor, Laboratório de Ultraestrutura Celular Hertha Meyer,
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro
CCS-Bloco G, Ilha do Fundão, Rio de Janeiro
Rio de Janeiro, 21941-900
Brasil


Thaïs Souto-Padrón Ph.D.
Professor, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro,
Ilha do Fundão
Rio de Janeiro, 21941-9000
Brasil


David A Campbell Ph.D.
Professor, Department of Microbiology
Immunology & Molecular Genetics, University of California
Los Angeles
California, 90095-1489
USA


David M. Engman M.D., Ph.D.
Professor, Departments of Pathology and Microbiology-Immunology
Northwestern University
Chicago
Illinois, 60611
USA


Conrad L. Epting M.D.
Assistant Professor, Department of Pediatrics
Chicago
Illinois, 60611
USA


Kevin M. Bonney B.S.
Researcher, Departments of Pathology and Microbiology-Immunology
Chicago
Illinois, 60611
USA


Maurício Martins Rodrigues M.D., Ph.D.
Associate Professor, Departamento de Microbiologia
Imunologia e Parasitologia
Universidade Federal de São Paulo-Escola Paulista de Medicina
São Paulo, 04044-010
Brazil


Bruna Cunha de Alencar
Research Assistant, Departamento de Microbiologia, Imunologia e Parasitologia
Universidade Federal de São Paulo-Escola Paulista de Medicina
São Paulo, 04044-010
Brazil


José Ronnie Vasconcelos Ph.D.
Research Assistant, Departemento de Imunologia
Instituto de Ciências Biomédicas, Univesidade de São Paulo
SP, 05508-900
Brasil


Fernando Pimentel
Research Assistant, Chagas Disease Multidisciplinary Research Laboratory
Faculty of Medicine, University of Brasilia
Federal District
Brasilia, 70.910-900
Brazil


Ciro Cordeiro
Research Assistant, Chagas Disease Multidisciplinary Research Laboratory
University of Brasilia
Faculty of Medicine, Federal District
Brasilia, 70.910-900
Brazil


Nadjar Nitz Ph.D.
Associate Professor, Chagas Disease Multidisciplinary Research Laboratory
Faculty of Medicine, University of Brasilia
Federal District
Brasilia, 70.910-900
Brazil


Mariana M. Hecht Ph.D.
Assistant Professor, Chagas Disease Multidisciplinary Research Laboraqtory
Faculty of Medicine, University of Brasilia
Federal District
Brasilia, 70.910-900
Brazil


Liana Lauria-Pires M.D., Ph.D.
Associate Professor, Chagas Disease Multidisciplinary Research Laboraqtory
Faculty of Medicine, University of Brasilia
Federal District
Brasilia, 70.910-900
Brazil


Ana de Cassia Rosa Ph.D.
Researcher, Chagas Disease Multidisciplinary Research Laboraqtory
Faculty of Medicine, University of Brasilia
Federal District
Brasilia, 70.910-900
Brazil


Cleudson Nery de Castro M.D., Ph.D.
Associate Professor, Núcleo de Medicina Tropical da Universidade de Brasilia
Federal District
Brasilia, 70.910-900
Brazil


Izabela M. Dourado Bastos Ph.D.
Associate Professor, Laboratory of Host-Parasite Interface
Institute of Biology/Faculty of Medicine
The University of Brasília
Brasília, 70910-900
Brazil


David Neves Ph.D.
Research Assistant, Laboratory of Host-Parasite Interface
Institute of Biology/Faculty of Medicine
The University of Brasília
Brasília, 70910-900
Brazil


Meire M. Lima Ph.D.
Research Assistant, Laboratory of Host-Parasite Interface
Institute of Biology/Faculty of Medicine
The University of Brasília
Brasília, 70910-900
Brazil


Jaime M. Santana, Ph.D.
Associate Professor, Laboratory of Host-Parasite Interface
Institute of Biology/Faculty of Medicine
The University of Brasília
Brasília, 70910-900
Brazil


Clever Gomes Ph.D.
Research Assistant, Chagas Disease Multidisciplinary Research Laboratory
Faculty of Medicine, University of Brasília
Federal District
Brasília, 70910-900
Brazil


Silene Lozzi Ph.D.
Associate Professor, Department of Genetics and Morphology
Institute of Biology, University of Brasilia
Federal District
Brasília, 70910-900
Brazil


Pedro Monteiro, Ph.D.
Associate Professor, Department of Nursery, Faculty of Health Sciences
University of Brasília
Federal District
Brasília, 70910-900
Brazil


Ana Bussacos Ph.D.
Research Assistant, Chagas Disease Multidisciplinary Research Laboratory, Faculty of Medicine
University of Brasília
Federal District
Brasília, 70910-900
Brazil


Concepta McManus M.V.D., Ph.D.
Associate Professor, Faculty of Veterinary Medicine
University of Brasilia
Federal District
Brasília, 70910-900
Brazil


Alessandro Sousa
Research Assistant, Chagas Disease Multidisciplinary Research Laboratory
Faculty of Medicine, University of Brasilia
Federal District
Brasília, 70910-900
Brazil




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