American Trypanosomiasis Chagas Disease, Second Edition: One Hundred Years of Research - American Trypanosomiasis Chagas Disease, Second Edition: One Hundred Years of Research -

Preface History of the discovery of the American Trypanosomiasis A beautiful history of life and work The history of a significant discovery Salvador Mazza: marked the history of the knowledge of his disease Cecilio Romanha: his contribution to the identification of the disease First evidence of Trypanosomiasis Americana (Chagas disease) in various countries of Latin America Chagas disease 100 years after the discovery Acknowledgments References Chagas disease in pre-Colombian civilizations Genetic variation Archeology Biochemistry (Bioarcheology)The parasite transmission cycle Insect vectors associated with the human habitats Historical overview Pre-Hispanic settlements in areas of transmission of T. cruzi Argentine-Bolivian Altiplano, Northwest Argentina Sierras Centrales Sur del Peru Meso-America, Mayan culture Andean region, Northern South America Oral infection by T. cruzi Evidence of human T. cruzi infection in pre-Colombian civilizations References Social and medical aspects on Chagas disease management and control General frame and costs of HCD The medical burden of HCD in endemic and nonendemic areas The particular question of specific treatment of Chagas disease Some social remarks concerning the control of HCD Final remarks Abbreviations References Current epidemiological trends of Chagas disease in Latin America and future challenges: epidemiology, surveillance, and health policies Modes of transmission Transmission through vectors Transmission via blood transfusion Methods and measurement of epidemiological trends in the continent from 1980 to 2006 Transmission through vectors Transmission through blood transfusion Feasibility of interruption of transmission Current control programs Economic impact Program costs and cost-effectiveness of control interventions Epidemiological impact in the region Initiative of the Southern Cone countries: epidemiological trends Initiative of the Andean countries: epidemiological trends Initiative of the Central American countries: epidemiological trends Amazon initiative Epidemiological impact Future challenges Transmission in the Amazon region Globalization of transmission Local epidemiological situations Political and structural factors References Geographical distribution of Chagas disease Vector phylogeography and ecology Parasite phylogeography and ecology Epidemiological implications of parasite distributions Vector-parasite-host interactions and implications for Chagas disease distribution Assessment of regions affected by Chagas disease Oceania and Asia Chagas disease in Mexico and Central America Chagas disease in the Amazon region Chagas disease in the Andean region Chagas disease in the Southern Cone countries References Classification and systematics of the Triatominae Subfamily: Triatominae Tribes and genera Tribe: Alberproseniini (genus Alberprosenia)Tribe: Bolboderini (genera: Bolbodera, Belminus, Microtriatoma, Parabelminus)Tribe: Cavernicolini (genus: Cavernicola)Tribe: Rhodniini (genera: Psammolestes, Rhodnius)Tribe: Triatomini (genera: Dipetalogaster, Eratyrus, Hermanlentia, Linshcosteus, Panstrongylus, Paratriatoma, Triatoma)Concept of species Historical concept Modern concepts Examples of specific questions Panstrongylus lignarius and P. herreri Conclusions The species level and the phylogenetic concepts The species level and the nonphylogenetic concepts A consensual approach to the species Recommendations Conclusion Acknowledgment References Biology of Triatominae General biology of vectors Active dispersion Passive dispersion Population dynamics Insight into the biology and ecology of Triatominae in the silvatic environment Interest of a trapping device Sylvatic habitat Access to host Survival strategy Vectorial capacity and domesticity Adaptation to Trypanosoma cruzi Blood feeding habits Vector control strategy Entomological surveillance Eradication, elimination, reduction Acknowledgments Glossary References Population genetics of Triatominae Vector population structure directs Chagas disease epidemiology and control Genetic variation, population structure, and implications for vector control Evolutionary forces and genetic variation Hardy- Weinberg equilibrium The neutral theory and statistical tests Spatial scale T. dimidiata R. prolixus Other species of Triatoma Perspective and future directions Acknowledgments References Geographic distribution of Triatominae vectors in America Limitation of sampling methods to estimate the geographic distribution of Triatominae Pattern of species richness in the New World Triatominae Distribution of Triatominae in the Americas Genus Rhodnius Genus Panstrongylus Genus Triatoma Triatoma dimidiata Other Triatoma of epidemiological importance Environmental variables as indicators of Triatominae geographic distribution Environmental variables and the distribution of T. infestans Environmental variables and the distribution of other Triatominae Global warming and expansion of geographic range of T infestans Glossary References Control strategies against Triatominae Elimination of domestic populations of Triatominae Multinational initiatives The beginning of the end?Criteria for stratification of vector control priorities Insecticide resistance New technologies for vector control The political commitment Acknowledgments References Ecological aspects of Trypanosoma [Ц cruzi: wild hosts and reservoirs Order Didelphimorphia Superorder Xenarthra Order Rodentia Order Primata Order Carnivora Order Chiroptera Order Artiodactyla References Trypanosoma cruzi enzootic cycle: general aspects, domestic and synanthropic hosts and reservoirs What are the Trypanosoma cruzi reservoirs?Importance of wild and synanthropic mammals in public health—Brazil Domestic mammalian species Domestic nonmammalian species Importance of infected domestic mammals on public health in Brazil Mixed infection References Veterinary aspects The various ways of infection of animals (and humans)The problem of diagnosis in animals Natural infections in domestic animals and livestock Experimental infections in livestock New cycles establish in the United States Conclusions References Experimental studies of Chagas disease in animal models Animal species used as experimental model in Chagas disease Primates autochthonous from the American continent Primates nonautochthonous from the Americas/American continent Conclusions References Classification and phylogeny of Trypanosoma cruzi Origin of trypanosomes and the relationship between T. cruzi and T brucei Relationships within the genus Trypanosoma Molecular phylogenetics and traditional taxonomy of mammalian trypanosomes The main groups of trypanosomes recognized in molecular phylogenetic analyses The origin of the T. cruzi clade Outlook Glossary References Biology of Trypanosoma cruzi and biological diversity Evolutionary stages Biological cycle Biology in the vertebrate host Cellular adhesion Cellular invasion and formation of the parasitophorous vacuole Trypomastigote—amastigote differentiation Amastigote—trypomastigote differentiation Biology in the invertebrate host Biological diversity of T. cruzi In the invertebrate vector Maintaining T. cruzi in the laboratory Acellular culture Cellular culture Successive and alternative passages in animals and vectors Glossary References Biochemistry of Trypanosoma Chemotherapy of Chagas disease Metabolic pathways in T. cruzi that could provide targets for drugs against Chagas disease Isoprenoid pathway Polyprenyl diphosphate synthases Protein prenylation Ergosterol synthesis Redox metabolism Deficient metabolic utilization of H202 in T. cruzi The trypanothione system Other thiols Superoxide dismutases Chemotherapeutic agents used against Chagas disease and redox metabolism Acidocalcisome biochemistry and osmoregulation The role of acidocalcisomes in T. cruzi metabolism Acidocalcisomes and osmoregulation in T. cruzi Acidocalcisomes as drug targets Conclusion Acknowledgments References Ultrastructure of Trypanosoma cruzi and its interaction with host cells Structural organization of Trypanosoma cruzi The nucleus The kinetoplast—mitochondrion complex The glycosome The acidocalcisome The contractile vacuole The cytoskeleton The flagellum The flagellar pocket The secretory pathway The endocytic pathway Other cytoplasmic structures The cell surface Fine structure of the interaction of T. cruzi with host cells Triggering of endocytosis Lysis of the parasitophorous vacuole (PV) membrane Acknowledgments References Genetics of Trypanosoma cruzi Sequencing strategy, genome organization, and content Comparative genome sequencing and analyses Comparative genome analysis with other trypanosomatids Transcription mechanisms and genetic expression in T cruzi Unique mechanisms of control of gene expression and gene expression profiling Genetic manipulation of T. cruzi References Kinetoplast genome Replication model of kDNA Maxicircles and minicircles: kDNA coding Determination of T. cruzi lineages analyzing minicircles DNA sequences References Experimental and natural recombination in Trypanosoma cruzi Genetic diversity of T. cruzi Experimental recombination Recombination in natural populations Inter-lineage (inter DTU) recombination: TcV and TcVI Interlineage (inter DTU) recombination: other lineages Mitochondrial introgression as a signature of genetic exchange Intralineage (infra DTU) recombination Conclusions and future research Acknowledgments References Trypanosoma cruzi and the model of predominant clonal evolution An indispensable recall of evolutionary genetics Predominant clonal evolution: what does it mean?T. cruzi undergoes some genetic exchange Comparing the information of different markers Erroneous concept: microsatellites cannot be used for phylogenetic reconstruction The results: how does T. cruzi evolve?Genetic variants of T. cruzi represent clonets, not clones Recombination operates at the evolutionary scale: reticulate evolution T. cruzi is a structured species The discrete typing units or "near-clades"Evolutionary origin of the hybrid near-clades Nomenclature considerations Medical and epidemiological characteristics of T. cruzi near-clades Relevance of T. cruzi genetic variability in applied research Conclusion: Trypanosoma cruzi should be a star in the field of pathogen population genetics Glossary of specialized terms References Vector transmission: how it works, what transmits, where it occurs How does transmission work?Who transmits the parasite?Vector capacity Eclectic species Chagas disease in the Amazonian region Where does the transmission occur?In dwellings In rural, urban, and periurban areas Risk factors of domiciliary infestation by triatomines Does vector transmission occur outside human dwellings?The perception of vectors and a need for education References Maternal-fetal transmission of Trypanosoma Routes of maternal—fetal transmission of Trypanosoma cruzi Possible transmission routes of Trypanosoma cruzi parasites The hematogenous transplacental route: strengths and weaknesses of the trophoblastic barrier Ex vivo/in vitro interactions between Trypanosoma cruzi and placenta Histopathologic studies of placentas from infected or uninfected neonates Interpretation attempt of Trypanosoma cruzi— placenta interactions Timing of maternal—fetal transmission of Trypanosoma cruzi Parasitic factors involved in transplacental transmission and development of Trypanosoma cruzi infection in fetuses/newborns Maternal factors involved in transmission and development of Trypanosoma cruzi infection Parasitic load during pregnancy and transmission of congenital infection Immunity in pregnant women and transmission of congenital infection Other maternal factors involved in transmission of congenital infection Interactions between the maternal and fetal immune systems Main biorelevant transferred molecules Maternal immunological imprinting/priming of infant immune responses Parasite amounts in newborns and severity of congenital Chagas disease Immune responses in newborns of Trypanosoma cruzi-infected mothers Interpretation attempt of fetal/neonatal immune responses to Trypanosoma cruzi Other fetal/neonatal factors susceptible to interfere with the development of congenital Chagas disease Vertical transmission of Trypanosoma cruzi in other mammals Vertical transmission in the natural mammal reservoir of Trypanosoma cruzi Vertical transmission in experimental infection with Trypanosoma cruzi Pregnancy outcomes, clinical manifestations, and long-term consequences of congenital Chagas disease Trypanosoma cruzi infection and pregnancy outcomes Clinical manifestations of congenital Chagas disease Long-term consequences of congenital infection with Trypanosoma cruzi Laboratory diagnosis of congenital infection with Trypanosoma cruzi Detection of infection in pregnant women In utero detection of fetal infection Detection of neonatal infection (0—4 weeks after birth)Infant detection of Trypanosoma cruzi congenital infection (1—12 months after birth)Recommendations Treatment of congenital infection with Trypanosoma cruzi Prevention and control of congenital Trypanosoma cruzi infection Conclusions References Other forms of transmission: blood transfusion, organ transplantation, laboratory accidents, oral and sexual transmission Blood transfusion Current situation in endemic countries Current situation in nonendemic countries Strategies to combat T. cruzi transmission risk through blood transfusion Organ transplantation Organ transplantation from T. cruzi-infected donors Organ transplantation in T. cruzi-infected recipients Laboratory-acquired contamination Oral transmission Experimental and natural infections of mammals via the oral route Human outbreaks of acute Chagas disease acquired by oral transmission Prevention of oral transmission Sexual transmission References Protective host response to Trypanosoma cruzi and its limitations Innate immune response in T. cruzi infection Soluble components of the innate system Innate recognition of T. cruzi infection Cells of the innate immune system Natural killer (NK) and other innate cells Neutrophils Monocytes/macrophages Macrophage activation Trypanocidal action of macrophages Modulation of immune responses by macrophages Macrophages as antigen-presenting cells Dendritic cells (DCs) and the initiation of the adaptive immune response Adaptive immune response: induction, characterization, and role of the T cell response T cell epitopes T lymphocytes in the control of the infection Regulatory T cells The recently disclosed role of IL-17 in T. cruzi infection Adaptive immune response: the B cell response and production of antibodies Deregulations of T and B lymphocyte responses Defective lymphocyte responses Polyclonal activation Escape mechanisms of T. cruzi to the immune responses Resistance to complement lysis Intracellular survival Escape from the action of Ab Being a stealth parasite, dampening and disturbing T cell responses Conclusion References Cell invasion by Trypanosoma cruzi and the type I interferon response Attachment to the host cell and parasite homing Nonphagocytic cell invasion by T. cruzi Lysosome exocytosis invasion route Plasma membrane invasion route The autophagosome route Toward a unified model for T. cruzi invasion Escape from the lysosome Global transcriptional responses to T. cruzi infection: type I IFN response Type I IFNs Signaling pathways involved in type I IFN production in T. cruzi infected cells Type I IFN responses to T. cruzi infection in the mouse model The balance between type I and type II IFN responses during infection with intracellular pathogens Concluding remarks Acknowledgments Glossary References Human genetic susceptibility to Chagas disease Phenotypes for study Heritability Candidate gene studies Genetic associations from candidate gene studies to date Focusing on the MHC class III region Chemokines and their receptors Cytokines and their receptors Other genes Genome-wide association studies The future References Clinical phases and forms of Chagas disease Acute phase Chronic phase Indeterminate form Cardiac form Digestive form Cardiodigestive form Concluding remarks Glossary References Diagnosis of Trypanosoma cruzi infection History of diagnosis in Chagas disease Diagnosis of T. cruzi infection Parasitological tests Acute phase (direct and concentration methods)Direct tests Other direct tests Concentration methods Microhematocrit Chronic phase Serological tests Antigenic makeup Antibody response Different serological tests The indirect hemagglutination test (IH)The direct agglutination test The indirect immunofluorescence (IIF)The immunoenzymatic test of ELISA (Enzyme-Linked ImmunoSorbent Assay)Western blot (including TESA-blot)Lytic assays including flow cytometry Chemiluminescence Rapid tests Crude preparations Purified antigens Recombinant proteins Synthetic peptides Different supports Filter paper Blood banks, serology, and quality control for Chagas disease Application of diagnostic tests in different contexts Parasitological and serological tests in the acute phase and reactivation Transmission by transfusion or transplantation Oral transmission Laboratory acquired infection Reactivation of chronically infected Tests in the chronic phase Confirmation of a clinical case Epidemiological surveys Follow up of specifically treated patients Quality control in serology Prophylaxis to avoid accidental contamination Future perspectives References AIDS and Chagas' disease БТЛ Epidemiology of Chagas' disease in Latin America and Argentina Natural history of Chagas' disease Pathogenic mechanisms of Chagas' disease reactivation in AIDS patients AIDS and Chagas' disease Clinical aspects Laboratory diagnosis Diagnosis of chagasic meningoencephalitis Diagnosis of chagasic tumor-like lesions Diagnosis of heart compromise Differential diagnosis Conclusion Glossary of specialized terms of this chapter References Treatment of Chagas disease Drugs which inhibit protein or purine synthesis Inhibitors of ergoesterol Inhibitors of trypanothione metabolism Inhibitors of cysteine protease (CPI)Inhibitors of phospholipids Inhibitors of pyrophosphate metabolism Natural drugs Other drugs Treatment of human infection Current drug therapy Acute cases Congenital infection Accidental Chagas disease Organ transplants Reactivations of chronic Chagas disease and treatment of Chagas disease in immunosuppressed patients Evaluation and follow-up of specific therapy Resistance of T. cruzi to drugs Critical comments Glossary References Vaccine development for Chagas disease 32 DNA vaccination in experimental models of Trypanosoma cruzi infection Vaccination with attenuated parasites (premunition)Basic laboratory studies on premunition against Typanosoma cruzi Field studies on premunition in guinea pigs and dogs Generation of attenuated parasites by genetic manipulation and their use as potential vaccines against Chagas disease Final considerations Acknowledgments