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

PrefaceHistory of the discovery of the American Trypanosomiasis A beautiful history of life and workThe history of a significant discoverySalvador Mazza: marked the history of the knowledge of his diseaseCecilio Romanha: his contribution to the identification of the diseaseFirst evidence of Trypanosomiasis Americana (Chagas disease) in various countries of Latin AmericaChagas disease 100 years after the discoveryAcknowledgmentsReferencesChagas disease in pre-Colombian civilizationsGenetic variationArcheologyBiochemistry (Bioarcheology)The parasite transmission cycleInsect vectors associated with the human habitatsHistorical overviewPre-Hispanic settlements in areas of transmission of T. cruziArgentine-Bolivian Altiplano, Northwest ArgentinaSierras CentralesSur del PeruMeso-America, Mayan cultureAndean region, Northern South AmericaOral infection by T. cruziEvidence of human T. cruzi infection in pre-Colombian civilizationsReferencesSocial and medical aspects on Chagas disease management and controlGeneral frame and costs of HCDThe medical burden of HCD in endemic and nonendemic areasThe particular question of specific treatment of Chagas diseaseSome social remarks concerning the control of HCDFinal remarksAbbreviationsReferencesCurrent epidemiological trends of Chagas disease in Latin America and future challenges: epidemiology, surveillance, and health policiesModes of transmissionTransmission through vectorsTransmission via blood transfusionMethods and measurement of epidemiological trends in the continent from 1980 to 2006Transmission through vectorsTransmission through blood transfusionFeasibility of interruption of transmissionCurrent control programsEconomic impactProgram costs and cost-effectiveness of control interventionsEpidemiological impact in the regionInitiative of the Southern Cone countries: epidemiological trendsInitiative of the Andean countries: epidemiological trendsInitiative of the Central American countries: epidemiological trendsAmazon initiativeEpidemiological impactFuture challengesTransmission in the Amazon regionGlobalization of transmissionLocal epidemiological situationsPolitical and structural factorsReferencesGeographical distribution of Chagas disease Vector phylogeography and ecologyParasite phylogeography and ecologyEpidemiological implications of parasite distributionsVector-parasite-host interactions and implications for Chagas disease distributionAssessment of regions affected by Chagas diseaseOceania and AsiaChagas disease in Mexico and Central AmericaChagas disease in the Amazon regionChagas disease in the Andean regionChagas disease in the Southern Cone countriesReferencesClassification and systematics of the Triatominae Subfamily: TriatominaeTribes and generaTribe: 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 speciesHistorical conceptModern conceptsExamples of specific questionsPanstrongylus lignarius and P. herreriConclusionsThe species level and the phylogenetic conceptsThe species level and the nonphylogenetic conceptsA consensual approach to the speciesRecommendationsConclusionAcknowledgmentReferencesBiology of TriatominaeGeneral biology of vectorsActive dispersionPassive dispersionPopulation dynamicsInsight into the biology and ecology of Triatominae in the silvatic environmentInterest of a trapping deviceSylvatic habitatAccess to hostSurvival strategyVectorial capacity and domesticityAdaptation to Trypanosoma cruziBlood feeding habitsVector control strategyEntomological surveillanceEradication, elimination, reductionAcknowledgmentsGlossaryReferencesPopulation genetics of Triatominae Vector population structure directs Chagas disease epidemiology and controlGenetic variation, population structure, and implications for vector controlEvolutionary forces and genetic variationHardy- Weinberg equilibriumThe neutral theory and statistical testsSpatial scaleT. dimidiataR. prolixusOther species of TriatomaPerspective and future directionsAcknowledgmentsReferencesGeographic distribution of Triatominae vectors in America Limitation of sampling methods to estimate the geographic distribution of TriatominaePattern of species richness in the New World TriatominaeDistribution of Triatominae in the AmericasGenus RhodniusGenus PanstrongylusGenus TriatomaTriatoma dimidiataOther Triatoma of epidemiological importanceEnvironmental variables as indicators of Triatominae geographic distributionEnvironmental variables and the distribution of T. infestansEnvironmental variables and the distribution of other TriatominaeGlobal warming and expansion of geographic range of T infestansGlossaryReferencesControl strategies against Triatominae Elimination of domestic populations of TriatominaeMultinational initiativesThe beginning of the end?Criteria for stratification of vector control prioritiesInsecticide resistanceNew technologies for vector controlThe political commitmentAcknowledgmentsReferencesEcological aspects of Trypanosoma [Ц cruzi: wild hosts and reservoirs Order DidelphimorphiaSuperorder XenarthraOrder RodentiaOrder PrimataOrder CarnivoraOrder ChiropteraOrder ArtiodactylaReferencesTrypanosoma cruzi enzootic cycle: general aspects, domestic and synanthropic hosts and reservoirsWhat are the Trypanosoma cruzi reservoirs?Importance of wild and synanthropic mammals in public health—BrazilDomestic mammalian speciesDomestic nonmammalian speciesImportance of infected domestic mammals on public health in BrazilMixed infectionReferencesVeterinary aspectsThe various ways of infection of animals (and humans)The problem of diagnosis in animalsNatural infections in domestic animals and livestockExperimental infections in livestockNew cycles establish in the United StatesConclusionsReferencesExperimental studies of Chagas disease in animal modelsAnimal species used as experimental model in Chagas diseasePrimates autochthonous from the American continentPrimates nonautochthonous from the Americas/American continentConclusionsReferencesClassification and phylogeny of Trypanosoma cruzi Origin of trypanosomes and the relationship between T. cruzi and T bruceiRelationships within the genus TrypanosomaMolecular phylogenetics and traditional taxonomy of mammalian trypanosomesThe main groups of trypanosomes recognized in molecular phylogenetic analysesThe origin of the T. cruzi cladeOutlookGlossaryReferencesBiology of Trypanosoma cruzi and biological diversity Evolutionary stagesBiological cycleBiology in the vertebrate hostCellular adhesionCellular invasion and formation of the parasitophorous vacuoleTrypomastigote—amastigote differentiationAmastigote—trypomastigote differentiationBiology in the invertebrate hostBiological diversity of T. cruziIn the invertebrate vectorMaintaining T. cruzi in the laboratoryAcellular cultureCellular cultureSuccessive and alternative passages in animals and vectorsGlossaryReferencesBiochemistry of Trypanosoma Chemotherapy of Chagas diseaseMetabolic pathways in T. cruzi that could provide targets for drugs against Chagas diseaseIsoprenoid pathwayPolyprenyl diphosphate synthasesProtein prenylationErgosterol synthesisRedox metabolismDeficient metabolic utilization of H202 in T. cruziThe trypanothione systemOther thiolsSuperoxide dismutasesChemotherapeutic agents used against Chagas disease and redox metabolismAcidocalcisome biochemistry and osmoregulationThe role of acidocalcisomes in T. cruzi metabolismAcidocalcisomes and osmoregulation in T. cruziAcidocalcisomes as drug targetsConclusionAcknowledgmentsReferencesUltrastructure of Trypanosoma cruzi and its interaction with host cellsStructural organization of Trypanosoma cruziThe nucleusThe kinetoplast—mitochondrion complexThe glycosomeThe acidocalcisomeThe contractile vacuoleThe cytoskeletonThe flagellumThe flagellar pocketThe secretory pathwayThe endocytic pathwayOther cytoplasmic structuresThe cell surfaceFine structure of the interaction of T. cruzi with host cellsTriggering of endocytosisLysis of the parasitophorous vacuole (PV) membraneAcknowledgmentsReferencesGenetics of Trypanosoma cruziSequencing strategy, genome organization, and contentComparative genome sequencing and analysesComparative genome analysis with other trypanosomatidsTranscription mechanisms and genetic expression in T cruziUnique mechanisms of control of gene expression and gene expression profilingGenetic manipulation of T. cruziReferencesKinetoplast genomeReplication model of kDNAMaxicircles and minicircles: kDNA codingDetermination of T. cruzi lineages analyzing minicircles DNA sequencesReferencesExperimental and natural recombination in Trypanosoma cruziGenetic diversity of T. cruziExperimental recombinationRecombination in natural populationsInter-lineage (inter DTU) recombination: TcV and TcVIInterlineage (inter DTU) recombination: other lineagesMitochondrial introgression as a signature of genetic exchangeIntralineage (infra DTU) recombinationConclusions and future researchAcknowledgmentsReferencesTrypanosoma cruzi and the model of predominant clonal evolution An indispensable recall of evolutionary geneticsPredominant clonal evolution: what does it mean?T. cruzi undergoes some genetic exchangeComparing the information of different markersErroneous concept: microsatellites cannot be used for phylogenetic reconstructionThe results: how does T. cruzi evolve?Genetic variants of T. cruzi represent clonets, not clonesRecombination operates at the evolutionary scale: reticulate evolutionT. cruzi is a structured speciesThe discrete typing units or "near-clades"Evolutionary origin of the hybrid near-cladesNomenclature considerationsMedical and epidemiological characteristics of T. cruzi near-cladesRelevance of T. cruzi genetic variability in applied researchConclusion: Trypanosoma cruzi should be a star in the field of pathogen population geneticsGlossary of specialized termsReferencesVector transmission: how it works, what transmits, where it occursHow does transmission work?Who transmits the parasite?Vector capacityEclectic speciesChagas disease in the Amazonian regionWhere does the transmission occur?In dwellingsIn rural, urban, and periurban areasRisk factors of domiciliary infestation by triatominesDoes vector transmission occur outside human dwellings?The perception of vectors and a need for educationReferencesMaternal-fetal transmission of TrypanosomaRoutes of maternal—fetal transmission of Trypanosoma cruziPossible transmission routes of Trypanosoma cruzi parasitesThe hematogenous transplacental route: strengths and weaknesses of the trophoblastic barrierEx vivo/in vitro interactions between Trypanosoma cruzi and placentaHistopathologic studies of placentas from infected or uninfected neonatesInterpretation attempt of Trypanosoma cruzi— placenta interactionsTiming of maternal—fetal transmission of Trypanosoma cruziParasitic factors involved in transplacental transmission and development of Trypanosoma cruzi infection in fetuses/newbornsMaternal factors involved in transmission and development of Trypanosoma cruzi infectionParasitic load during pregnancy and transmission of congenital infectionImmunity in pregnant women and transmission of congenital infectionOther maternal factors involved in transmission of congenital infectionInteractions between the maternal and fetal immune systemsMain biorelevant transferred moleculesMaternal immunological imprinting/priming of infant immune responsesParasite amounts in newborns and severity of congenital Chagas diseaseImmune responses in newborns of Trypanosoma cruzi-infected mothersInterpretation attempt of fetal/neonatal immune responses to Trypanosoma cruziOther fetal/neonatal factors susceptible to interfere with the development of congenital Chagas diseaseVertical transmission of Trypanosoma cruzi in other mammalsVertical transmission in the natural mammal reservoir of Trypanosoma cruziVertical transmission in experimental infection with Trypanosoma cruziPregnancy outcomes, clinical manifestations, and long-term consequences of congenital Chagas diseaseTrypanosoma cruzi infection and pregnancy outcomesClinical manifestations of congenital Chagas diseaseLong-term consequences of congenital infection with Trypanosoma cruziLaboratory diagnosis of congenital infection with Trypanosoma cruziDetection of infection in pregnant womenIn utero detection of fetal infectionDetection of neonatal infection (0—4 weeks after birth)Infant detection of Trypanosoma cruzi congenital infection (1—12 months after birth)RecommendationsTreatment of congenital infection with Trypanosoma cruziPrevention and control of congenital Trypanosoma cruzi infectionConclusionsReferencesOther forms of transmission: blood transfusion, organ transplantation, laboratory accidents, oral and sexual transmissionBlood transfusionCurrent situation in endemic countriesCurrent situation in nonendemic countriesStrategies to combat T. cruzi transmission risk through blood transfusionOrgan transplantationOrgan transplantation from T. cruzi-infected donorsOrgan transplantation in T. cruzi-infected recipientsLaboratory-acquired contaminationOral transmissionExperimental and natural infections of mammals via the oral routeHuman outbreaks of acute Chagas disease acquired by oral transmissionPrevention of oral transmissionSexual transmissionReferencesProtective host response to Trypanosoma cruzi and its limitationsInnate immune response in T. cruzi infectionSoluble components of the innate systemInnate recognition of T. cruzi infectionCells of the innate immune systemNatural killer (NK) and other innate cellsNeutrophilsMonocytes/macrophagesMacrophage activationTrypanocidal action of macrophagesModulation of immune responses by macrophagesMacrophages as antigen-presenting cellsDendritic cells (DCs) and the initiation of the adaptive immune responseAdaptive immune response: induction, characterization, and role of the T cell responseT cell epitopesT lymphocytes in the control of the infectionRegulatory T cellsThe recently disclosed role of IL-17 in T. cruzi infectionAdaptive immune response: the B cell response and production of antibodiesDeregulations of T and B lymphocyte responsesDefective lymphocyte responsesPolyclonal activationEscape mechanisms of T. cruzi to the immune responsesResistance to complement lysisIntracellular survivalEscape from the action of AbBeing a stealth parasite, dampening and disturbing T cell responsesConclusionReferencesCell invasion by Trypanosoma cruzi and the type I interferon responseAttachment to the host cell and parasite homingNonphagocytic cell invasion by T. cruziLysosome exocytosis invasion routePlasma membrane invasion routeThe autophagosome routeToward a unified model for T. cruzi invasionEscape from the lysosomeGlobal transcriptional responses to T. cruzi infection: type I IFN responseType I IFNsSignaling pathways involved in type I IFN production in T. cruzi infected cellsType I IFN responses to T. cruzi infection in the mouse modelThe balance between type I and type II IFN responses during infection with intracellular pathogensConcluding remarksAcknowledgmentsGlossaryReferencesHuman genetic susceptibility to Chagas disease Phenotypes for studyHeritabilityCandidate gene studiesGenetic associations from candidate gene studies to dateFocusing on the MHC class III regionChemokines and their receptorsCytokines and their receptorsOther genesGenome-wide association studiesThe futureReferencesClinical phases and forms of Chagas disease Acute phaseChronic phaseIndeterminate formCardiac formDigestive formCardiodigestive formConcluding remarksGlossaryReferencesDiagnosis of Trypanosoma cruzi infection History of diagnosis in Chagas diseaseDiagnosis of T. cruzi infectionParasitological testsAcute phase (direct and concentration methods)Direct testsOther direct testsConcentration methodsMicrohematocritChronic phaseSerological testsAntigenic makeupAntibody responseDifferent serological testsThe indirect hemagglutination test (IH)The direct agglutination testThe indirect immunofluorescence (IIF)The immunoenzymatic test of ELISA (Enzyme-Linked ImmunoSorbent Assay)Western blot (including TESA-blot)Lytic assays including flow cytometryChemiluminescenceRapid testsCrude preparationsPurified antigensRecombinant proteinsSynthetic peptidesDifferent supportsFilter paperBlood banks, serology, and quality control for Chagas diseaseApplication of diagnostic tests in different contextsParasitological and serological tests in the acute phase and reactivationTransmission by transfusion or transplantationOral transmissionLaboratory acquired infectionReactivation of chronically infectedTests in the chronic phaseConfirmation of a clinical caseEpidemiological surveysFollow up of specifically treated patientsQuality control in serologyProphylaxis to avoid accidental contaminationFuture perspectivesReferencesAIDS and Chagas' disease БТЛEpidemiology of Chagas' disease in Latin America and ArgentinaNatural history of Chagas' diseasePathogenic mechanisms of Chagas' disease reactivation in AIDS patientsAIDS and Chagas' diseaseClinical aspectsLaboratory diagnosisDiagnosis of chagasic meningoencephalitisDiagnosis of chagasic tumor-like lesionsDiagnosis of heart compromiseDifferential diagnosisConclusionGlossary of specialized terms of this chapterReferencesTreatment of Chagas disease Drugs which inhibit protein or purine synthesisInhibitors of ergoesterolInhibitors of trypanothione metabolismInhibitors of cysteine protease (CPI)Inhibitors of phospholipidsInhibitors of pyrophosphate metabolismNatural drugsOther drugsTreatment of human infectionCurrent drug therapyAcute casesCongenital infectionAccidental Chagas diseaseOrgan transplantsReactivations of chronic Chagas disease and treatment of Chagas disease in immunosuppressed patientsEvaluation and follow-up of specific therapyResistance of T. cruzi to drugsCritical commentsGlossaryReferencesVaccine development for Chagas disease 32DNA vaccination in experimental models of Trypanosoma cruzi infectionVaccination with attenuated parasites (premunition)Basic laboratory studies on premunition against Typanosoma cruziField studies on premunition in guinea pigs and dogsGeneration of attenuated parasites by genetic manipulation and their use as potential vaccines against Chagas diseaseFinal considerationsAcknowledgments
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