4,038
Views
131
CrossRef citations to date
0
Altmetric
Review

Between a bug and a hard place: Trypanosoma cruzi genetic diversity and the clinical outcomes of Chagas disease

, &

References

  • WHO. Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Wkly Epidemiol Rec 2015;90:33-44
  • Lent H, Wygodzinsky P. Revision of the Triatominae (Hemiptera, Reduviidae), and their significance as vectors of Chagas’ disease. Bull Am Mus Nat Hist 1979;63:123-520
  • Galvao C, Carcavallo R, Rocha Dda S, Jurberg J. A checklist of the current valid species of the subfamily Triatominae Jeannel, 1919 (Hemiptera, Reduviidae, Triatominae) and their geographical distribution with nomenclatural and taxonomic notes. Zootaxa 2003;202:1-36
  • Noireau F, Diosque P, Jansen AM. Trypanosoma cruzi: adaptation to its vectors and its hosts. Vet Res 2009;40:26
  • Coura JR, Dias JC. Epidemiology, control and surveillance of Chagas disease: 100 years after its discovery. Mem Inst Oswaldo Cruz 2009;104(Suppl 1):31-40
  • Shikanai-Yasuda MA, Carvalho NB. Oral transmission of Chagas disease. Clin Infect Dis 2012;54:845-52
  • Gurtler RE. Sustainability of vector control strategies in the Gran Chaco Region: current challenges and possible approaches. Mem Inst Oswaldo Cruz 2009;104(Suppl 1):52-59
  • Bern C, Martin DL, Gilman RH. Acute and congenital Chagas disease. Adv Parasitol 2011;75:19-47
  • Jackson Y, Getaz L, Wolff H, et al. Prevalence, clinical staging and risk for blood-borne transmission of Chagas disease among Latin American migrants in Geneva. Switzerland. Plos Negl Trop Dis 2010;4:e592
  • Centers for disease control and prevention. Chagas disease after organ transplantation–Los Angeles, California, 2006. Morb Mortal Wkly Rep 2006;55:798-800
  • Rassi AJr, Rassi A, Marin-Neto JA. Chagas disease. Lancet 2010;375:1388-402
  • Maguire JH, Hoff R, Sherlock I, et al. Cardiac morbidity and mortality due to Chagas’ disease: prospective electrocardiographic study of a Brazilian community. Circulation 1987;75:1140-5
  • Rassi AJr, Rassi A, Little WC. Chagas’ heart disease. Clin Cardiol 2000;23:883-9
  • Rassi AJr, Rassi SG, Rassi A. Sudden death in Chagas’ disease. Arq Bras Cardiol 2001;76:75-96
  • de Oliveira RB, Troncon LE, Dantas RO, Menghelli UG. Gastrointestinal manifestations of Chagas’ disease. Am J Gastroenterol 1998;93:884-9
  • Miles MA, Cedillos RA, Povoa MM, et al. Do radically dissimilar Trypanosoma cruzi strains (zymodemes) cause Venezuelan and Brazilian forms of Chagas’ disease? Lancet 1981;1:1338-40
  • Rezende JMF. Chagasic mega syndromes and regional differences In: New Approaches in American Trypanosomiasis Research: Proceedings of an International Symposium, Belo Horizonte, Minas Gerais, Brazil. 18-21 March 1975. Washington, DC: Pan American Health Organization, 1976
  • Bern C, Montgomery SP, Herwaldt BL, et al. Evaluation and treatment of Chagas disease in the United States: a systematic review. JAMA 2007;298:2171-81
  • Gascon J, Albajar P, Canas E, et al. [Diagnosis, management and treatment of chronic Chagas’ heart disease in areas where Trypanosoma cruzi infection is not endemic]. Enferm Infecc Microbiol Clin 2008;26:99-106
  • Ministério da Saúde Brasil. [Brazilian Consensus on Chagas disease]. Rev Soc Bras Med Trop 2005;38(Suppl 3):7-29
  • Acquatella H. Echocardiography in Chagas heart disease. Circulation 2007;115:1124-31
  • Carrasco HA, Barboza JS, Inglessis G, et al. Left ventricular cineangiography in Chagas’ disease: detection of early myocardial damage. Am Heart J 1982;104:595-602
  • Hunt SA. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2005;46:e1-82
  • Kuschnir E, Sgammini H, Castro R, et al. [Evaluation of cardiac function by radioisotopic angiography, in patients with chronic Chagas cardiopathy]. Arq Bras Cardiol 1985;45:249-56
  • Hidron A, Gilman R, Justiniano J, et al. Chagas cardiomyopathy in the context of the chronic disease transition. Plos Negl Trop Dis 2010;4:e688
  • Rocha MO, Ribeiro AL, Teixeira MM. Clinical management of chronic Chagas cardiomyopathy. Front Biosci 2003;8:e44-54
  • Sabino EC, Ribeiro AL, Salemi VM, et al. Ten-year incidence of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-seropositive former blood donors. Circulation 2013;127:1105-15
  • Le VV, Wheeler MT, Mandic S, et al. Addition of the electrocardiogram to the preparticipation examination of college athletes. Clin J Sport Med 2010;20:98-105
  • Rassi AJr, Rassi A, Rassi SG. Predictors of mortality in chronic Chagas disease: a systematic review of observational studies. Circulation 2007;115:1101-8
  • Lewis MD, Llewellyn MS, Yeo M, et al. Recent, independent and anthropogenic origins of Trypanosoma cruzi hybrids. Plos Negl Trop Dis 2011;5:e1363
  • Zingales B, Andrade SG, Briones MR, et al. A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI. Mem Inst Oswaldo Cruz 2009;104:1051-4
  • Marcili A, Lima L, Cavazzana M, et al. A new genotype of Trypanosoma cruzi associated with bats evidenced by phylogenetic analyses using SSU rDNA, cytochrome b and Histone H2B genes and genotyping based on ITS1 rDNA. Parasitology 2009;136:641-55
  • Pinto CM, Kalko EK, Cottontail I, et al. TcBat a bat-exclusive lineage of Trypanosoma cruzi in the Panama Canal Zone, with comments on its classification and the use of the 18S rRNA gene for lineage identification. Infect Genet Evol 2012;12:1328-32
  • Ramirez JD, Tapia-Calle G, Munoz-Cruz G, et al. Trypanosome species in neo-tropical bats: biological, evolutionary and epidemiological implications. Infect Genet Evol 2014;22:250-6
  • Zingales B, Miles MA, Campbell DA, et al. The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infect Genet Evol 2012;12:240-53
  • Miles MA, Toye PJ, Oswald SC, Godfrey DG. The identification by isoenzyme patterns of two distinct strain-groups of Trypanosoma cruzi, circulating independently in a rural area of Brazil. Trans R Soc Trop Med Hyg 1977;71:217-25
  • Miles MA, Souza A, Povoa M, et al. Isozymic heterogeneity of Trypanosoma cruzi in the first autochthonous patients with Chagas’ disease in Amazonian Brazil. Nature 1978;272:819-21
  • Tibayrenc M, Ayala FJ. Isoenzyme variability in Trypanosoma cruzi, the agent of Chagas’ disease. Genetical, taxonomical and epidemiological significance. Evolution 1988;42:277-92
  • Tibayrenc M, Neubauer K, Barnabe C, et al. Genetic characterization of six parasitic protozoa: parity between random-primer DNA typing and multilocus enzyme electrophoresis. Proc Natl Acad Sci U S A 1993;90:1335-9
  • Steindel M, Dias Neto E, de Menezes CL, et al. Random amplified polymorphic DNA analysis of Trypanosoma cruzi strains. Mol Biochem Parasitol 1993;60:71-9
  • Souto RP, Fernandes O, Macedo AM, et al. DNA markers define two major phylogenetic lineages of Trypanosoma cruzi. Mol Biochem Parasitol 1996;83:141-52
  • Fernandes O, Souto RP, Castro JA, et al. Brazilian isolates of Trypanosoma cruzi from humans and triatomines classified into two lineages using mini-exon and ribosomal RNA sequences. Am J Trop Med Hyg 1998;58:807-11
  • Fernandes O, Sturm NR, Derre R, Campbell DA. The mini-exon gene: a genetic marker for zymodeme III of Trypanosoma cruzi. Mol Biochem Parasitol 1998;95:129-33
  • Anonymous Recommendations from a satellite meeting. Mem Inst Oswaldo Cruz 1999;94(Suppl 1):429-32
  • Brisse S, Barnabe C, Tibayrenc M. Identification of six Trypanosoma cruzi phylogenetic lineages by random amplified polymorphic DNA and multilocus enzyme electrophoresis. Int J Parasitol 2000;30:35-44
  • Brisse S, Verhoef J, Tibayrenc M. Characterisation of large and small subunit rRNA and mini-exon genes further supports the distinction of six Trypanosoma cruzi lineages. Int J Parasitol 2001;31:1218-26
  • Tibayrenc M. Genetic epidemiology of parasitic protozoa and other infectious agents: the need for an integrated approach. Int J Parasitol 1998;28:85-104
  • Herrera C, Bargues MD, Fajardo A, et al. Identifying four Trypanosoma cruzi I isolate haplotypes from different geographic regions in Colombia. Infect Genet Evol 2007;7:535-9
  • Herrera C, Guhl F, Falla A, et al. Genetic variability and phylogenetic relationships within Trypanosoma cruzi I isolated in Colombia based on miniexon gene sequences. J Parasitol Res 2009;2009: Article ID 897364:9
  • Falla A, Herrera C, Fajardo A, et al. Haplotype identification within Trypanosoma cruzi I in Colombian isolates from several reservoirs, vectors and humans. Acta Trop 2009;110:15-21
  • Cura CI, Mejia-Jaramillo AM, Duffy T, et al. Trypanosoma cruzi I genotypes in different geographical regions and transmission cycles based on a microsatellite motif of the intergenic spacer of spliced-leader genes. Int J Parasitol 2010;40:1599-607
  • Zumaya-Estrada FA, Messenger LA, Lopez-Ordonez T, et al. North American import? Charting the origins of an enigmatic Trypanosoma cruzi domestic genotype. Parasit Vectors 2012;5:226
  • Ramirez JD, Guhl F, Messenger LA, et al. Contemporary cryptic sexuality in Trypanosoma cruzi. Mol Ecol 2012;21:4216-26
  • de Freitas JM, Augusto-Pinto L, Pimenta JR, et al. Ancestral genomes, sex, and the population structure of Trypanosoma cruzi. Plos Pathog 2006;2:e24
  • Devera R, Fernandes O, Coura JR. Should Trypanosoma cruzi be called ‘cruzi’ complex? a review of the parasite diversity and the potential of selecting population after in vitro culturing and mice infection. Mem Inst Oswaldo Cruz 2003;98:1-12
  • Guhl F, Ramirez JD. Trypanosoma cruzi I diversity: towards the need of genetic subdivision? Acta Trop 2011;119:1-4
  • Westenberger SJ, Barnabe C, Campbell DA, Sturm NR. Two hybridization events define the population structure of Trypanosoma cruzi. Genetics 2005;171:527-43
  • Ramirez JD, Llewellyn MS. Reproductive clonality in protozoan pathogens - truth or artefact? Mol Ecol 2014;23:4195-202
  • Tibayrenc M, Ayala FJ. How clonal are Trypanosoma and Leishmania? Trends Parasitol 2013;29:264-9
  • Machado CA, Ayala FJ. Nucleotide sequences provide evidence of genetic exchange among distantly related lineages of Trypanosoma cruzi. Proc Natl Acad Sci U S A 2001;98:7396-401
  • Yeo M, Mauricio IL, Messenger LA, et al. Multilocus sequence typing (MLST) for lineage assignment and high resolution diversity studies in Trypanosoma cruzi. Plos Negl Trop Dis 2011;5:e1049
  • Brisse S, Henriksson J, Barnabe C, et al. Evidence for genetic exchange and hybridization in Trypanosoma cruzi based on nucleotide sequences and molecular karyotype. Infect Genet Evol 2003;2:173-83
  • Miles MA, Llewellyn MS, Lewis MD, et al. The molecular epidemiology and phylogeography of Trypanosoma cruzi and parallel research on Leishmania: looking back and to the future. Parasitology 2009;136:1509-28
  • Lima VS, Xavier SC, Maldonado IF, et al. Expanding the knowledge of the geographic distribution of Trypanosoma cruzi TcII and TcV/TcVI genotypes in the Brazilian Amazon. Plos One 2014;9:e116137
  • Ramirez JD, Guhl F, Rendon LM, et al. Chagas cardiomyopathy manifestations and Trypanosoma cruzi genotypes circulating in chronic Chagasic patients. Plos Negl Trop Dis 2010;4:e899
  • Carrasco HJ, Segovia M, Llewellyn MS, et al. Geographical distribution of Trypanosoma cruzi genotypes in Venezuela. Plos Negl Trop Dis 2012;6:e1707
  • Anez N, Crisante G, da Silva FM, et al. Predominance of lineage I among Trypanosoma cruzi isolates from Venezuelan patients with different clinical profiles of acute Chagas’ disease. Trop Med Int Health 2004;9:1319-26
  • Roellig DM, Brown EL, Barnabe C, et al. Molecular typing of Trypanosoma cruzi isolates, United States. Emerg Infect Dis 2008;14:1123-5
  • Barnabe C, Brisse S, Tibayrenc M. Population structure and genetic typing of Trypanosoma cruzi, the agent of Chagas disease: a multilocus enzyme electrophoresis approach. Parasitology 2000;120(Pt 5):513-526
  • Llewellyn MS, Miles MA, Carrasco HJ, et al. Genome-scale multilocus microsatellite typing of Trypanosoma cruzi discrete typing unit I reveals phylogeographic structure and specific genotypes linked to human infection. Plos Pathog 2009;5:e1000410
  • Gaunt M, Miles M. The ecotopes and evolution of triatomine bugs (triatominae) and their associated trypanosomes. Mem Inst Oswaldo Cruz 2000;95:557-65
  • Arenas M, Campos R, Coronado X, et al. Trypanosoma cruzi genotypes of insect vectors and patients with Chagas of Chile studied by means of cytochrome b gene sequencing, minicircle hybridization, and nuclear gene polymorphisms. Vector Borne Zoonotic Dis 2012;12:196-205
  • Barnabe C, De Meeus T, Noireau F, et al. Trypanosoma cruzi discrete typing units (DTUs): microsatellite loci and population genetics of DTUs TcV and TcI in Bolivia and Peru. Infect Genet Evol 2011;11:1752-60
  • Cortez MR, Pinho AP, Cuervo P, et al. Trypanosoma cruzi (Kinetoplastida Trypanosomatidae): ecology of the transmission cycle in the wild environment of the Andean valley of Cochabamba, Bolivia. Exp Parasitol 2006;114:305-13
  • Breniere SF, Aliaga C, Waleckx E, et al. Genetic characterization of Trypanosoma cruzi DTUs in wild Triatoma infestans from Bolivia: predominance of TcI. Plos Negl Trop Dis 2012;6:e1650
  • Cecere MC, Cardinal MV, Arrabal JP, et al. Microcavia australis (Caviidae, Rodentia), a new highly competent host of Trypanosoma cruzi I in rural communities of northwestern Argentina. Acta Trop 2015;142:34-40
  • Messenger LA, Garcia L, Vanhove M, et al. Ecological host fitting of Trypanosoma cruzi TcI in Bolivia: mosaic population structure, hybridization and a role for humans in Andean parasite dispersal. Mol Ecol 2015;24:2406-22
  • Lima VS, Jansen AM, Messenger LA, et al. Wild Trypanosoma cruzi I genetic diversity in Brazil suggests admixture and disturbance in parasite populations from the Atlantic Forest region. Parasit Vectors 2014;7:263
  • Fernandes O, Mangia RH, Lisboa CV, et al. The complexity of the sylvatic cycle of Trypanosoma cruzi in Rio de Janeiro state (Brazil) revealed by the non-transcribed spacer of the mini-exon gene. Parasitology 1999;118(Pt 2):161-166
  • Lisboa CV, Pinho AP, Monteiro RV, Jansen AM. Trypanosoma cruzi (kinetoplastida Trypanosomatidae): biological heterogeneity in the isolates derived from wild hosts. Exp Parasitol 2007;116:150-5
  • Araujo CA, Waniek PJ, Xavier SC, Jansen AM. Genotype variation of Trypanosoma cruzi isolates from different Brazilian biomes. Exp Parasitol 2011;127:308-12
  • Maffey L, Cardinal MV, Ordonez-Krasnowski PC, et al. Direct molecular identification of Trypanosoma cruzi discrete typing units in domestic and peridomestic Triatoma infestans and Triatoma sordida from the Argentine Chaco. Parasitology 2012;139:1570-9
  • Fernandez MD, Cecere MC, Lanati LA, et al. Geographic variation of Trypanosoma cruzi discrete typing units from Triatoma infestans at different spatial scales. Acta Trop 2014;140C:10-18
  • Enriquez GF, Cardinal MV, Orozco MM, et al. Discrete typing units of Trypanosoma cruzi identified in rural dogs and cats in the humid Argentinean Chaco. Parasitology 2013;140:303-8
  • Cardinal MV, Lauricella MA, Ceballos LA, et al. Molecular epidemiology of domestic and sylvatic Trypanosoma cruzi infection in rural northwestern Argentina. Int J Parasitol 2008;38(13):1533-43
  • Garzon EA, Barnabe C, Cordova X, et al. Trypanosoma cruzi isoenzyme variability in Ecuador: first observation of zymodeme III genotypes in chronic chagasic patients. Trans R Soc Trop Med Hyg 2002;96:378-82
  • Guhl F, Ramirez JD. Retrospective molecular integrated epidemiology of Chagas disease in Colombia. Infect Genet Evol 2013;20:148-54
  • Yeo M, Acosta N, Llewellyn M, et al. Origins of Chagas disease: Didelphis species are natural hosts of Trypanosoma cruzi I and armadillos hosts of Trypanosoma cruzi II, including hybrids. Int J Parasitol 2005;35:225-33
  • Llewellyn MS, Lewis MD, Acosta N, et al. Trypanosoma cruzi IIc: phylogenetic and phylogeographic insights from sequence and microsatellite analysis and potential impact on emergent Chagas disease. Plos Negl Trop Dis 2009;3:e510
  • Marcili A, Lima L, Valente VC, et al. Comparative phylogeography of Trypanosoma cruzi TCIIc: new hosts, association with terrestrial ecotopes, and spatial clustering. Infect Genet Evol 2009;9:1265-74
  • Orozco MM, Enriquez GF, Alvarado-Otegui JA, et al. New sylvatic hosts of Trypanosoma cruzi and their reservoir competence in the humid Chaco of Argentina: a longitudinal study. Am J Trop Med Hyg 2013;88:872-82
  • Morocoima A, Carrasco HJ, Boadas J, et al. Trypanosoma cruzi III from armadillos (Dasypus novemcinctus novemcinctus) from Northeastern Venezuela and its biological behavior in murine model. Risk of emergence of Chagas’ disease. Exp Parasitol 2012;132:341-7
  • Valente SA, da Costa Valente V, das Neves Pinto AY, et al. Analysis of an acute Chagas disease outbreak in the Brazilian Amazon: human cases, triatomines, reservoir mammals and parasites. Trans R Soc Trop Med Hyg 2009;103:291-7
  • Lewis MD, Ma J, Yeo M, et al. Genotyping of Trypanosoma cruzi: systematic selection of assays allowing rapid and accurate discrimination of all known lineages. Am J Trop Med Hyg 2009;81:1041-9
  • Marcili A, Valente VC, Valente SA, et al. Trypanosoma cruzi in Brazilian Amazonia: Lineages TCI and TCIIa in wild primates, Rhodnius spp. and in humans with Chagas disease associated with oral transmission. Int J Parasitol 2009;39:615-23
  • Roellig DM, Savage MY, Fujita AW, et al. Genetic variation and exchange in Trypanosoma cruzi isolates from the United States. Plos One 2013;8:e56198
  • Monteiro WM, Magalhaes LK, de Sa AR, et al. Trypanosoma cruzi IV causing outbreaks of acute Chagas disease and infections by different haplotypes in the Western Brazilian Amazonia. Plos One 2012;7:e41284
  • Roque AL, Xavier SC, da Rocha MG, et al. Trypanosoma cruzi transmission cycle among wild and domestic mammals in three areas of orally transmitted Chagas disease outbreaks. Am J Trop Med Hyg 2008;79:742-9
  • Monteiro WM, Magalhaes LK, Santana Filho FS, et al. Trypanosoma cruzi TcIII/Z3 genotype as agent of an outbreak of Chagas disease in the Brazilian Western Amazonia. Trop Med Int Health 2010;15:1049-51
  • Monje-Rumi MM, Brandan CP, Ragone PG, et al. Trypanosoma cruzi diversity in the Gran Chaco: mixed infections and differential host distribution of TcV and TcVI. Infect Genet Evol 2015;29:53-9
  • Ramirez JD, Hernandez C, Montilla M, et al. First Report of Human Trypanosoma cruzi Infection Attributed to TcBat Genotype. Zoonoses Public Health 2014;61:477-9
  • Vago AR, Andrade LO, Leite AA, et al. Genetic characterization of Trypanosoma cruzi directly from tissues of patients with chronic Chagas disease: differential distribution of genetic types into diverse organs. Am J Pathol 2000;156:1805-9
  • Burgos JM, Begher S, Silva HM, et al. Molecular identification of Trypanosoma cruzi I tropism for central nervous system in Chagas reactivation due to AIDS. Am J Trop Med Hyg 2008;78:294-7
  • Burgos JM, Diez M, Vigliano C, et al. Molecular identification of Trypanosoma cruzi discrete typing units in end-stage chronic Chagas heart disease and reactivation after heart transplantation. Clin Infect Dis 2010;51:485-95
  • Bosseno MF, Telleria J, Vargas F, et al. Trypanosoma cruzi: study of the distribution of two widespread clonal genotypes in Bolivian Triatoma infestans vectors shows a high frequency of mixed infections. Exp Parasitol 1996;83:275-82
  • Yeo M, Lewis MD, Carrasco HJ, et al. Resolution of multiclonal infections of Trypanosoma cruzi from naturally infected triatomine bugs and from experimentally infected mice by direct plating on a sensitive solid medium. Int J Parasitol 2007;37:111-20
  • Llewellyn MS, Rivett-Carnac JB, Fitzpatrick S, et al. Extraordinary Trypanosoma cruzi diversity within single mammalian reservoir hosts implies a mechanism of diversifying selection. Int J Parasitol 2011;41:609-14
  • Rocha FL, Roque AL, de Lima JS, et al. Trypanosoma cruzi infection in neotropical wild carnivores (Mammalia: Carnivora): at the top of the T. cruzi transmission chain. Plos One 2013;8:e67463
  • Nouvellet P, Dumonteil E, Gourbiere S. The improbable transmission of Trypanosoma cruzi to human: the missing link in the dynamics and control of Chagas disease. Plos Negl Trop Dis 2013;7:e2505
  • da Silveira Pinto A, de Lana M, Britto C, et al. Experimental Trypanosoma cruzi biclonal infection in Triatoma infestans: detection of distinct clonal genotypes using kinetoplast DNA probes. Int J Parasitol 2000;30:843-8
  • Pinto AS, de Lana M, Bastrenta B, et al. Compared vectorial transmissibility of pure and mixed clonal genotypes of Trypanosoma cruzi in Triatoma infestans. Parasitol Res 1998;84:348-53
  • Martins HR, Silva RM, Valadares HM, et al. Impact of dual infections on chemotherapeutic efficacy in BALB/c mice infected with major genotypes of Trypanosoma cruzi. Antimicrob Agents Chemother 2007;51:3282-9
  • Araujo CA, Waniek PJ, Jansen AM. TcI/TcII co-infection can enhance Trypanosoma cruzi growth in Rhodnius prolixus. Parasit Vectors 2014;7:94
  • Gaunt MW, Yeo M, Frame IA, et al. Mechanism of genetic exchange in American trypanosomes. Nature 2003;421:936-9
  • Oberle M, Balmer O, Brun R, Roditi I. Bottlenecks and the maintenance of minor genotypes during the life cycle of Trypanosoma brucei. Plos Pathog 2010;6:e1001023
  • Valadares HM, Pimenta JR, Segatto M, et al. Unequivocal identification of subpopulations in putative multiclonal Trypanosoma cruzi strains by FACs single cell sorting and genotyping. Plos Negl Trop Dis 2012;6:e1722
  • Messenger LA, Yeo M, Lewis MD, et al. Molecular Genotyping of Trypanosoma cruzi for Lineage Assignment and Population Genetics. Methods Mol Biol 2015;1201:297-337
  • Ramirez JD, Herrera C, Bogota Y, et al. Validation of a Poisson-distributed limiting dilution assay (LDA) for a rapid and accurate resolution of multiclonal infections in natural Trypanosoma cruzi populations. J Microbiol Methods 2013;92:220-5
  • Dvorak JA, Hartman DL, Miles MA. Trypanosoma cruzi: Correlation of Growth Kinetics to Zymodeme Type in Clones Derived from Various Sources. J Protozool 1980;27:472-4
  • Alves AM, De Almeida DF, von Kruger WM. Changes in Trypanosoma cruzi kinetoplast DNA minicircles induced by environmental conditions and subcloning. J Eukaryot Microbiol 1994;41:415-19
  • Alves AM, Tanuri A, de Almeida DF, von Kruger WM. Reversible changes in the isoenzyme electrophoretic mobility pattern and infectivity in clones of Trypanosoma cruzi. Exp Parasitol 1993;77:246-53
  • Engel JC, Dvorak JA, Segura EL, Crane MS. Trypanosoma cruzi: biological characterization of 19 clones derived from two chronic chagasic patients. I. Growth kinetics in liquid medium. J Protozool 1982;29:555-60
  • Deane MP, Mangia RH, Pereira NM, et al. Trypanosoma cruzi: strain selection by different schedules of mouse passage of an initially mixed infection. Mem Inst Oswaldo Cruz 1984;79:495-7
  • Deane MP, Sousa MA, Pereira NM, et al. Trypanosoma cruzi: inoculation schedules and re-isolation methods select individual strains from doubly infected mice, as demonstrated by schizodeme and zymodeme analyses. J Protozool 1984;31:276-80
  • Morel CM, Deane MP, Goncalves AM. The complexity of Trypanosoma cruzi populations revealed by schizodeme analysis. Parasitol Today 1986;2:97-101
  • Deane MP, Jansen AM, Mangia RH, et al. Are our laboratory ‘strains’ representative samples of Trypanosoma cruzi populations that circulate in nature? Mem Inst Oswaldo Cruz 1984;79(Suppl.):19-24
  • Siriano Lda R, Luquetti AO, Avelar JB, et al. Chagas disease: increased parasitemia during pregnancy detected by hemoculture. Am J Trop Med Hyg 2011;84:569-74
  • Miles MA, Apt BW, Widmer G, et al. Isozyme heterogeneity and numerical taxonomy of Trypanosoma cruzi stocks from Chile. Trans R Soc Trop Med Hyg 1984;78:526-35
  • Luquetti AO, Miles MA, Rassi A, et al. Trypanosoma cruzi: zymodemes associated with acute and chronic Chagas’ disease in central Brazil. Trans R Soc Trop Med Hyg 1986;80:462-70
  • Ortiz S, Zulantay I, Apt W, et al. Transferability of Trypanosoma cruzi from mixed human host infection to Triatoma infestans and from insects to axenic culture. Parasitol Int 2015;64:33-6
  • Sanchez LV, Bautista DC, Corredor AF, et al. Temporal variation of Trypanosoma cruzi discrete typing units in asymptomatic Chagas disease patients. Microbes Infect 2013;15:745-8
  • Diosque P, Tomasini N, Lauthier JJ, et al. Optimized multilocus sequence typing (MLST) scheme for Trypanosoma cruzi. Plos Negl Trop Dis 2014;8:e3117
  • Oliveira RP, Broude NE, Macedo AM, et al. Probing the genetic population structure of Trypanosoma cruzi with polymorphic microsatellites. Proc Natl Acad Sci U S A 1998;95:3776-80
  • Oliveira RP, Melo AI, Macedo AM, et al. The population structure of Trypanosoma cruzi: expanded analysis of 54 strains using eight polymorphic CA-repeat microsatellites. Mem Inst Oswaldo Cruz 1999;94(Suppl I):65-70
  • Burgos JM, Altcheh J, Bisio M, et al. Direct molecular profiling of minicircle signatures and lineages of Trypanosoma cruzi bloodstream populations causing congenital Chagas disease. Int J Parasitol 2007;37:1319-27
  • Morel C, Chiari E, Camargo EP, et al. Strains and clones of Trypanosoma cruzi can be characterized by pattern of restriction endonuclease products of kinetoplast DNA minicircles. Proc Natl Acad Sci U S A 1980;77:6810-14
  • Telleria J, Lafay B, Virreira M, et al. Trypanosoma cruzi: sequence analysis of the variable region of kinetoplast minicircles. Exp Parasitol 2006;114:279-88
  • Velazquez M, Diez CN, Mora C, et al. Trypanosoma cruzi: an analysis of the minicircle hypervariable regions diversity and its influence on strain typing. Exp Parasitol 2008;120:235-41
  • Veas F, Cuny G, Breniere SF, Tibayrenc M. Subspecific kDNA probes for major clones of Trypanosoma cruzi. Acta Trop 1990;48:79-82
  • Macedo AM, Machado CR, Oliveira RP, Pena SD. Trypanosoma cruzi: genetic structure of populations and relevance of genetic variability to the pathogenesis of chagas disease. Mem Inst Oswaldo Cruz 2004;99:1-12
  • Macedo AM, Oliveira RP, Pena SD. Chagas disease: role of parasite genetic variation in pathogenesis. Expert Rev Mol Med 2002;4:1-16
  • Dvorak JA, Hall TE, Crane MS, et al. Trypanosoma cruzi: flow cytometric analysis. I. Analysis of total DNA/organism by means of mithramycin-induced fluorescence. J Protozool 1982;29:430-7
  • Lewis MD, Llewellyn MS, Gaunt MW, et al. Flow cytometric analysis and microsatellite genotyping reveal extensive DNA content variation in Trypanosoma cruzi populations and expose contrasts between natural and experimental hybrids. Int J Parasitol 2009;39:1305-17
  • Henriksson J, Pettersson U, Solari A. Trypanosoma cruzi: correlation between karyotype variability and isoenzyme classification. Exp Parasitol 1993;77:334-48
  • Lima FM, Souza RT, Santori FR, et al. Interclonal variations in the molecular karyotype of Trypanosoma cruzi: chromosome rearrangements in a single cell-derived clone of the G strain. Plos One 2013;8:e63738
  • Henriksson J, Aslund L, Macina RA, et al. Chromosomal localization of seven cloned antigen genes provides evidence of diploidy and further demonstration of karyotype variability in Trypanosoma cruzi. Mol Biochem Parasitol 1990;42:213-23
  • Vargas N, Pedroso A, Zingales B. Chromosomal polymorphism, gene synteny and genome size in T. cruzi I and T. cruzi II groups. Mol Biochem Parasitol 2004;138:131-41
  • Souza RT, Lima FM, Barros RM, et al. Genome size, karyotype polymorphism and chromosomal evolution in Trypanosoma cruzi. Plos One 2011;6:e23042
  • O’Connor O, Bosseno MF, Barnabe C, et al. Genetic clustering of Trypanosoma cruzi I lineage evidenced by intergenic miniexon gene sequencing. Infect Genet Evol 2007;7:587-93
  • Wagner W, So M. Genomic variation of Trypanosoma cruzi: involvement of multicopy genes. Infect Immun 1990;58:3217-24
  • Moreira OC, Ramirez JD, Velazquez E, et al. Towards the establishment of a consensus real-time qPCR to monitor Trypanosoma cruzi parasitemia in patients with chronic Chagas disease cardiomyopathy: a substudy from the BENEFIT trial. Acta Trop 2013;125:23-31
  • Schijman AG, Bisio M, Orellana L, et al. International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients. Plos Negl Trop Dis 2011;5:e931
  • Segatto M, Rodrigues CM, Machado CR, et al. LSSP-PCR of Trypanosoma cruzi: how the single primer sequence affects the kDNA signature. BMC Res Notes 2013;6:174
  • Pedroso A, Cupolillo E, Zingales B. Trypanosoma cruzi: exploring the nuclear genome of zymodeme 3 stocks by chromosome size polymorphism. Exp Parasitol 2007;116:71-6
  • Henriksson J, Dujardin JC, Barnabe C, et al. Chromosomal size variation in Trypanosoma cruzi is mainly progressive and is evolutionarily informative. Parasitology 2002;124:277-86
  • Macedo AM, Martins MS, Chiari E, Pena SD. DNA fingerprinting of Trypanosoma cruzi: a new tool for characterization of strains and clones. Mol Biochem Parasitol 1992;55:147-53
  • Ocana-Mayorga S, Llewellyn MS, Costales JA, et al. Sex, subdivision, and domestic dispersal of Trypanosoma cruzi lineage I in Southern Ecuador. Plos Negl Trop Dis 2010;4:e915
  • Cosentino RO, Aguero F. A simple strain typing assay for Trypanosoma cruzi: discrimination of major evolutionary lineages from a single amplification product. Plos Negl Trop Dis 2012;6:e1777
  • Weatherly DB, Boehlke C, Tarleton RL. Chromosome level assembly of the hybrid Trypanosoma cruzi genome. BMC Genomics 2009;10:255
  • Franzen O, Ochaya S, Sherwood E, et al. Shotgun sequencing analysis of Trypanosoma cruzi I Sylvio X10/1 and comparison with T. cruzi VI CL Brener. Plos Negl Trop Dis 2011;5:e984
  • Aslett M, Aurrecoechea C, Berriman M, et al. TriTrypDB: a functional genomic resource for the Trypanosomatidae. Nucleic Acids Res 2010;38:D457-62
  • El-Sayed NM, Myler PJ, Bartholomeu DC, et al. The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 2005;309:409-15
  • Downing T, Imamura H, Decuypere S, et al. Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. Genome Res 2011;21:2143-56
  • Rogers MB, Downing T, Smith BA, et al. Genomic confirmation of hybridisation and recent inbreeding in a vector-isolated Leishmania population. Plos Genet 2014;10:e1004092
  • Goodhead I, Capewell P, Bailey JW, et al. Whole-genome sequencing of Trypanosoma brucei reveals introgression between subspecies that is associated with virulence. MBio 2013;4(4):e00197-13
  • Campbell DA, Westenberger SJ, Sturm NR. The determinants of Chagas disease: connecting parasite and host genetics. Curr Mol Med 2004;4:549-62
  • Manoel-Caetano Fda S, Silva AE. Implications of genetic variability of Trypanosoma cruzi for the pathogenesis of Chagas disease. Cad Saude Publica 2007;23:2263-74
  • Virreira M, Truyens C, Alonso-Vega C, et al. Comparison of Trypanosoma cruzi lineages and levels of parasitic DNA in infected mothers and their newborns. Am J Trop Med Hyg 2007;77:102-6
  • Ortiz S, Zulantay I, Solari A, et al. Presence of Trypanosoma cruzi in pregnant women and typing of lineages in congenital cases. Acta Trop 2012;124:243-6
  • Miles MA, Lanham SM, de Souza AA, Povoa M. Further enzymic characters of Trypanosoma cruzi and their evaluation for strain identification. Trans R Soc Trop Med Hyg 1980;74:221-37
  • Andrade SG, Magalhaes JB. Biodemes and zymodemes of Trypanosoma cruzi strains: correlations with clinical data and experimental pathology. Rev Soc Bras Med Trop 1996;30:27-35
  • Rassi A, Porto CC, Rezende JM. Doença de Chagas. In: Doença Transmissiveis. Rio de Janeiro: Guanabara Koogan; 1979
  • Barrett TV, Hoff RH, Mott KE, et al. Epidemiological aspects of three Trypanosoma cruzi zymodemes in Bahia State, Brazil. Trans R Soc Trop Med Hyg 1980;74:84-90
  • Breniere SF, Carrasco R, Revollo S, et al. Chagas’ disease in Bolivia: clinical and epidemiological features and zymodeme variability of Trypanosoma cruzi strains isolated from patients. Am J Trop Med Hyg 1989;41:521-9
  • Apt W, Arribada A, Aguilera X, Sandoval J. Chagas’ cardiopathy and Trypanosoma cruzi zymodemes in Chile. Bull Pan Am Health Organ 1987;21:358-68
  • Apt W, Aguilera X, Arribada A, et al. Epidemiology of Chagas’ disease in northern Chile: isozyme profiles of Trypanosoma cruzi from domestic and sylvatic transmission cycles and their association with cardiopathy. Am J Trop Med Hyg 1987;37:302-7
  • Montamat EE, De Luca D’Oro GM, Gallerano RH, et al. Characterization of Trypanosoma cruzi populations by zymodemes: correlation with clinical picture. Am J Trop Med Hyg 1996;55:625-8
  • Montamat EE, De Luca d’Oro G, Perret B, Rivas C. Characterization of Trypanosoma cruzi from Argentina by electrophoretic zymograms. Acta Trop 1992;50:125-33
  • Lanham SM, Grendon JM, Miles MA, et al. A comparison of electrophoretic methods for isoenzyme characterization of trypanosomatids. I:Standard stocks of Trypanosoma cruzi zymodemes from northeast Brazil. Trans R Soc Trop Med Hyg 1981;75:742-50
  • Montamat EE, Arauzo S, Cazzulo JJ, Subias E. Characterization by electrophoretic zymograms of 19 Trypanosoma cruzi clones derived from two chronic chagasic patients. Comp Biochem Physiol B 1987;87:417-22
  • Tibayrenc M, Cariou ML, Solignac M, et al. New electrophoretic evidence of genetic variation and diploidy in Trypanosoma cruzi, the causative agent of Chagas’ disease. Genetica 1985;67:223-30
  • Santana RA, Magalhaes LK, Magalhaes LK, et al. Trypanosoma cruzi strain TcI is associated with chronic Chagas disease in the Brazilian Amazon. Parasit Vectors 2014;7:267
  • Gonzalez CI, Ortiz S, Solari A. Colombian Trypanosoma cruzi major genotypes circulating in patients: minicircle homologies by cross-hybridization analysis. Int J Parasitol 2010;40:1685-92
  • Zafra G, Mantilla JC, Jacome J, et al. Direct analysis of genetic variability in Trypanosoma cruzi populations from tissues of Colombian chagasic patients. Hum Pathol 2011;42:1159-68
  • Ruiz-Sanchez R, Leon MP, Matta V, et al. Trypanosoma cruzi isolates from Mexican and Guatemalan acute and chronic chagasic cardiopathy patients belong to Trypanosoma cruzi I. Mem Inst Oswaldo Cruz 2005;100:281-3
  • Martinez I, Nogueda B, Martinez-Hernandez F, Espinoza B. Microsatellite and mini-exon analysis of Mexican human DTU I Trypanosoma cruzi strains and their susceptibility to nifurtimox and benznidazole. Vector Borne Zoonotic Dis 2013;13:181-7
  • Sousa OE, Samudio F, de Junca C, Calzada JE. Molecular characterization of human Trypanosoma cruzi isolates from endemic areas in Panama. Mem Inst Oswaldo Cruz 2006;101:455-7
  • Cura CI, Lucero RH, Bisio M, et al. Trypanosoma cruzi discrete typing units in Chagas disease patients from endemic and non-endemic regions of Argentina. Parasitology 2012;139:516-21
  • del Puerto R, Nishizawa JE, Kikuchi M, et al. Lineage analysis of circulating Trypanosoma cruzi parasites and their association with clinical forms of Chagas disease in Bolivia. Plos Negl Trop Dis 2010;4:e687
  • D’Avila DA, Macedo AM, Valadares HM, et al. Probing population dynamics of Trypanosoma cruzi during progression of the chronic phase in chagasic patients. J Clin Microbiol 2009;47:1718-25
  • Lages-Silva E, Ramirez LE, Pedrosa AL, et al. Variability of kinetoplast DNA gene signatures of Trypanosoma cruzi II strains from patients with different clinical forms of Chagas’ disease in Brazil. J Clin Microbiol 2006;44:2167-71
  • Virreira M, Serrano G, Maldonado L, Svoboda M. Trypanosoma cruzi: typing of genotype (sub)lineages in megacolon samples from bolivian patients. Acta Trop 2006;100:252-5
  • Freitas JM, Lages-Silva E, Crema E, et al. Real time PCR strategy for the identification of major lineages of Trypanosoma cruzi directly in chronically infected human tissues. Int J Parasitol 2005;35:411-17
  • Di Noia JM, Buscaglia CA, De Marchi CR, et al. A Trypanosoma cruzi small surface molecule provides the first immunological evidence that Chagas’ disease is due to a single parasite lineage. J Exp Med 2002;195:401-13
  • Risso MG, Sartor PA, Burgos JM, et al. Immunological identification of Trypanosoma cruzi lineages in human infection along the endemic area. Am J Trop Med Hyg 2011;84:78-84
  • Bhattacharyya T, Falconar AK, Luquetti AO, et al. Development of peptide-based lineage-specific serology for chronic Chagas disease: geographical and clinical distribution of epitope recognition. Plos Negl Trop Dis 2014;8:e2892
  • Venegas J, Conoepan W, Pichuantes S, et al. Differential distribution of Trypanosoma cruzi clones in human chronic chagasic cardiopathic and non-cardiopathic individuals. Acta Trop 2009;109:187-93
  • Venegas J, Miranda S, Conoepan W, et al. Microsatellite marker analysis shows differentiation among Trypanosoma cruzi populations of peripheral blood and dejections of Triatoma infestans fed on the same chronic chagasic patients : microsatellite marker analysis and T. cruzi. Parasitol Res 2010;107:855-63
  • Venegas J, Diaz F, Rojas T, et al. Microsatellite loci-based distribution of Trypanosoma cruzi genotypes from Chilean chronic Chagas disease patients and Triatoma infestans is concordant with a specific host-parasite association hypothesis. Acta Parasitol 2013;58:139-48
  • Virreira M, Alonso-Vega C, Solano M, et al. Congenital Chagas disease in Bolivia is not associated with DNA polymorphism of Trypanosoma cruzi. Am J Trop Med Hyg 2006;75:871-9
  • Bern C. Chagas disease in the immunosuppressed host. Curr Opin Infect Dis 2012;25:450-7
  • Schenone H, Gaggero M, Sapunar J, et al. Congenital Chagas disease of second generation in Santiago, Chile. Report of two cases. Rev Inst Med Trop Sao Paulo 2001;43:231-2
  • Oliveira I, Torrico F, Munoz J, Gascon J. Congenital transmission of Chagas disease: a clinical approach. Expert Rev Anti Infect Ther 2010;8:945-56
  • Torrico F, Alonso-Vega C, Suarez E, et al. Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected newborns in Bolivia. Am J Trop Med Hyg 2004;70:201-9
  • Bern C, Verastegui M, Gilman RH, et al. Congenital Trypanosoma cruzi transmission in Santa Cruz. Bolivia. Clin Infect Dis 2009;49:1667-74
  • Bittencourt AL, Barbosa HS, Rocha T, et al. [Incidence of congenital transmission of Chagas’ disease in premature births in the Maternidade Tsylla Balbino (Salvador. Bahia)]. Rev Inst Med Trop Sao Paulo 1972;14:131-4
  • Torrico MC, Solano M, Guzman JM, et al. [Estimation of the parasitemia in Trypanosoma cruzi human infection: high parasitemias are associated with severe and fatal congenital Chagas disease]. Rev Soc Bras Med Trop 2005;38(Suppl 2):58-61
  • Dao L. Otros casos de enfermedad de Chagas en el Estado Guarico (Venezuela). Formas agudas e cronicas. Observacion sobre enfermedad de Chagas congenita. Revista Policlinica. Caracas 1949;17:17-32
  • Chagas C. Nova trypanozomiaze humana. Estudos sobre a morfologia e ciclo evolutivo do Schizotripanum cruzi n. gen. n. sp., agente etiologico de nova entidade morbida do homem. Mem Inst Oswaldo Cruz 1909;1:159-218
  • Bittencourt AL. Placentite chagasica e transmissao congenita da doenca de Chagas. Rev Inst Med Trop Sao Paulo 1963;5:62-7
  • de Rissio AM, Riarte AR, Garcia MM, et al. Congenital Trypanosoma cruzi infection. Efficacy of its monitoring in an urban reference health center in a non-endemic area of Argentina. Am J Trop Med Hyg 2010;82:838-45
  • Blanco SB, Segura EL, Cura EN, et al. Congenital transmission of Trypanosoma cruzi: an operational outline for detecting and treating infected infants in north-western Argentina. Trop Med Int Health 2000;5:293-301
  • Mallimaci MC, Sosa-Estani S, Russomando G, et al. Early diagnosis of congenital Trypanosoma cruzi infection, using shed acute phase antigen, in Ushuaia, Tierra del Fuego. Argentina. Am J Trop Med Hyg 2010;82:55-9
  • Bua J, Volta BJ, Perrone AE, et al. How to improve the early diagnosis of Trypanosoma cruzi infection: relationship between validated conventional diagnosis and quantitative DNA amplification in congenitally infected children. Plos Negl Trop Dis 2013;7:e2476
  • Azogue E, Darras C. [Prospective study of Chagas disease in newborn children with placental infection caused by Trypanosoma cruzi (Santa Cruz-Bolivia)]. Rev Soc Bras Med Trop 1991;24:105-9
  • Salas Clavijo NA, Postigo JR, Schneider D, et al. Prevalence of Chagas disease in pregnant women and incidence of congenital transmission in Santa Cruz de la Sierra. Bolivia. Acta Trop 2012;124:87-91
  • Rassi A, Amato Neto V, Rassi GG, et al. [A retrospective search for maternal transmission of Chagas infection from patients in the chronic phase]. Rev Soc Bras Med Trop 2004;37:485-9
  • Martins-Melo FR, Lima MS, Ramos ANJ, et al. Prevalence of Chagas disease in pregnant women and congenital transmission of Trypanosoma cruzi in Brazil: a systematic review and meta-analysis. Trop Med Int Health 2014;19:943-57
  • Apt W, Zulantay I, Solari A, et al. Vertical transmission of Trypanosoma cruzi in the Province of Choapa, IV Region, Chile: Preliminary Report (2005-2008). Biol Res 2010;43:269-74
  • Tello P, Fernandez P, Sandoval L, et al. [Incidence of Trypanosoma cruzi infection in mothers and sons in a section of the northern area of Santiago]. Bol Chil Parasitol 1982;37:23-4
  • Apt W, Zulantay I, Arnello M, et al. Congenital infection by Trypanosoma cruzi in an endemic area of Chile: a multidisciplinary study. Trans R Soc Trop Med Hyg 2013;107:98-104
  • Russomando G, de Tomassone MM, de Guillen I, et al. Treatment of congenital Chagas’ disease diagnosed and followed up by the polymerase chain reaction. Am J Trop Med Hyg 1998;59:487-91
  • Russomando G, Almiron M, Candia N, et al. [Implementation and evaluation of a locally sustainable system of prenatal diagnosis to detect cases of congenital Chagas disease in endemic areas of Paraguay]. Rev Soc Bras Med Trop 2005;38(Suppl 2):49-54
  • Hermann E, Truyens C, Alonso-Vega C, et al. Congenital transmission of Trypanosoma cruzi is associated with maternal enhanced parasitemia and decreased production of interferon- gamma in response to parasite antigens. J Infect Dis 2004;189:1274-81
  • Vekemans J, Truyens C, Torrico F, et al. Maternal Trypanosoma cruzi infection upregulates capacity of uninfected neonate cells To produce pro- and anti-inflammatory cytokines. Infect Immun 2000;68:5430-4
  • Freilij H, Altcheh J, Muchinik G. Perinatal human immunodeficiency virus infection and congenital Chagas’ disease. Pediatr Infect Dis J 1995;14:161-2
  • Scapellato PG, Bottaro EG, Rodriguez-Brieschke MT. Mother-child transmission of Chagas disease: could coinfection with human immunodeficiency virus increase the risk? Rev Soc Bras Med Trop 2009;42:107-9
  • Buekens P, Cafferata ML, Alger J, et al. Congenital transmission of Trypanosoma cruzi in Argentina, Honduras and Mexico: study protocol. Reprod Health 2013;10:55
  • Costales JA, Sanchez-Gomez A, Silva-Aycaguer LC, et al. A national survey to determine prevalence of Trypanosoma cruzi infection among pregnant women in Ecuador. Am J Trop Med Hyg 2015; In press
  • del Puerto F, Sanchez Z, Nara E, et al. Trypanosoma cruzi lineages detected in congenitally infected infants and Triatoma infestans from the same disease-endemic region under entomologic surveillance in Paraguay. Am J Trop Med Hyg 2010;82:386-90
  • Diez C, Lorenz V, Ortiz S, et al. Genotyping of Trypanosoma cruzi sublineage in human samples from a North-East Argentina area by hybridization with DNA probes and specific polymerase chain reaction (PCR). Am J Trop Med Hyg 2010;82:67-73
  • Carlier Y, Torrico F. Congenital infection with Trypanosoma cruzi: from mechanisms of transmission to strategies for diagnosis and control. Rev Soc Bras Med Trop 2003;36:767-71
  • Alonso-Vega C, Billot C, Torrico F. Achievements and challenges upon the implementation of a program for national control of congenital Chagas in Bolivia: results 2004-2009. Plos Negl Trop Dis 2013;7:e2304
  • Bisio M, Seidenstein ME, Burgos JM, et al. Urbanization of congenital transmission of Trypanosoma cruzi: prospective polymerase chain reaction study in pregnancy. Trans R Soc Trop Med Hyg 2011;105:543-9
  • Sanchez Negrette O, Mora MC, Basombrio MA. High prevalence of congenital Trypanosoma cruzi infection and family clustering in Salta. Argentina. Pediatrics 2005;115:e668-72
  • Andrade SG. The influence of the strain of Trypanosoma cruzi in placental infections in mice. Trans R Soc Trop Med Hyg 1982;76:123-8
  • Rendell VR, Gilman RH, Valencia E, et al. Trypanosoma cruzi-infected pregnant women without vector exposure have higher parasitemia levels: implications for congenital transmission risk. Plos One 2015;10:e0119527
  • Roellig DM, Ellis AE, Yabsley MJ. Oral transmission of Trypanosoma cruzi with opposing evidence for the theory of carnivory. J Parasitol 2009;95:360-4
  • Beltrao B, Cerroni P, Freitas DR, et al. Investigation of two outbreaks of suspected oral transmission of acute Chagas disease in the Amazon region, Para State, Brazil, in 2007. Trop Doct 2009;39:231-2
  • Blanchet D, Breniere SF, Schijman AG, et al. First report of a family outbreak of Chagas disease in French Guiana and posttreatment follow-up. Infect Genet Evol 2014;28:245-50
  • Nobrega AA, Garcia MH, Tatto E, et al. Oral transmission of Chagas disease by consumption of acai palm fruit, Brazil. Emerg Infect Dis 2009;15:653-5
  • Pinto AY, Harada GS, Valente V, et al. [Cardiac attacks in patients with acute Chagas disease in a family micro-outbreak, in Abaetetuba, Brazilian Amazon]. Rev Soc Bras Med Trop 2001;34:413-19
  • Steindel M, Kramer Pacheco L, Scholl D, et al. Characterization of Trypanosoma cruzi isolated from humans, vectors, and animal reservoirs following an outbreak of acute human Chagas disease in Santa Catarina State, Brazil. Diagn Microbiol Infect Dis 2008;60:25-32
  • de Noya B, Diaz-Bello Z, Colmenares C, et al. Large urban outbreak of orally acquired acute Chagas disease at a school in Caracas, Venezuela. J Infect Dis 2010;201:1308-15
  • Segovia M, Carrasco HJ, Martinez CE, et al. Molecular epidemiologic source tracking of orally transmitted Chagas disease, Venezuela. Emerg Infect Dis 2013;19:1098-101
  • Andrade SG, Campos RF, Steindel M, et al. Biological, biochemical and molecular features of Trypanosoma cruzi strains isolated from patients infected through oral transmission during a 2005 outbreak in the state of Santa Catarina, Brazil: its correspondence with the new T. cruzi Taxonomy Consensus (2009). Mem Inst Oswaldo Cruz 2011;106:948-56
  • Coura JR, Junqueira AC, Fernandes O, et al. Emerging Chagas disease in Amazonian Brazil. Trends Parasitol 2002;18:171-6
  • Marques J, Mendoza I, Noya B, et al. ECG manifestations of the biggest outbreak of Chagas disease due to oral infection in Latin-America. Arq Bras Cardiol 2013;101:249-54
  • Bastos CJ, Aras R, Mota G, et al. Clinical outcomes of thirteen patients with acute chagas disease acquired through oral transmission from two urban outbreaks in northeastern Brazil. Plos Negl Trop Dis 2010;4:e711
  • Diaz-Bello Z, Thomas MC, Lopez MC, et al. Trypanosoma cruzi genotyping supports a common source of infection in a school-related oral outbreak of acute Chagas disease in Venezuela. Epidemiol Infect 2014;142:156-62
  • Ramirez JD, Montilla M, Cucunuba ZM, et al. Molecular epidemiology of human oral Chagas disease outbreaks in Colombia. Plos Negl Trop Dis 2013;7:e2041
  • Soto H, Tibaduiza T, Montilla M, et al. [Investigation of vectors and reservoirs in an acute Chagas outbreak due to possible oral transmission in Aguachica, Cesar, Colombia]. Cad Saude Publica 2014;30:746-56
  • Villa LM, Guhl F, Zabala D, et al. The identification of two Trypanosoma cruzi I genotypes from domestic and sylvatic transmission cycles in Colombia based on a single polymerase chain reaction amplification of the spliced-leader intergenic region. Mem Inst Oswaldo Cruz 2013;108:932-5
  • Muñoz-Calderón A, Diaz-Bello Z, Valladares B, et al. Oral transmission of Chagas disease: typing of Trypanosoma cruzi from five outbreaks occurred in Venezuela shows multiclonal and common infections in patients, vectors and reservoirs. Infect Genet Evol 2013;17:113-22
  • Shikanai-Yasuda MA, Marcondes CB, Guedes LA, et al. Possible oral transmission of acute Chagas’ disease in Brazil. Rev Inst Med Trop Sao Paulo 1991;33:351-7
  • Covarrubias C, Cortez M, Ferreira D, Yoshida N. Interaction with host factors exacerbates Trypanosoma cruzi cell invasion capacity upon oral infection. Int J Parasitol 2007;37:1609-16
  • Yoshida N. Trypanosoma cruzi infection by oral route: how the interplay between parasite and host components modulates infectivity. Parasitol Int 2008;57:105-9
  • Yoshida N, Tyler KM, Llewellyn MS. Invasion mechanisms among emerging food-borne protozoan parasites. Trends Parasitol 2011;27:459-66
  • Camandaroba EL, Pinheiro Lima CM, Andrade SG. Oral transmission of Chagas disease: importance of Trypanosoma cruzi biodeme in the intragastric experimental infection. Rev Inst Med Trop Sao Paulo 2002;44:97-103
  • WHO Expert Committee. Control of Chagas Disease. Brasilia, Brazil: WHO; 2002
  • Verani JR, Seitz A, Gilman RH, et al. Geographic variation in the sensitivity of recombinant antigen-based rapid tests for chronic Trypanosoma cruzi infection. Am J Trop Med Hyg 2009;80:410-15
  • Umezawa ES, Luquetti AO, Levitus G, et al. Serodiagnosis of chronic and acute Chagas’ disease with Trypanosoma cruzi recombinant proteins: results of a collaborative study in six Latin American countries. J Clin Microbiol 2004;42:449-52
  • Caballero ZC, Sousa OE, Marques WP, et al. Evaluation of serological tests to identify Trypanosoma cruzi infection in humans and determine cross-reactivity with Trypanosoma rangeli and Leishmania spp. Clin Vaccine Immunol 2007;14:1045-9
  • Sosa-Estani S, Gamboa-Leon MR, Del Cid-Lemus J, et al. Use of a rapid test on umbilical cord blood to screen for Trypanosoma cruzi infection in pregnant women in Argentina, Bolivia, Honduras, and Mexico. Am J Trop Med Hyg 2008;79:755-9
  • Martin DL, Marks M, Galdos-Cardenas G, et al. Regional variation in the correlation of antibody and T-cell responses to Trypanosoma cruzi. Am J Trop Med Hyg 2014;90:1074-81
  • Cancado JR, Brener Z. Terapeutica. In: Trypanosoma cruzi e doença de Chagas. Rio de Janeiro, Brazil: Guanabara Koogan; 1979
  • Maia da Silva F, Rodrigues AC, Campaner M, et al. Randomly amplified polymorphic DNA analysis of Trypanosoma rangeli and allied species from human, monkeys and other sylvatic mammals of the Brazilian Amazon disclosed a new group and a species-specific marker. Parasitology 2004;128:283-94
  • A Study of the Use of Oral Posaconazole (POS) in the Treatment of Asymptomatic Chronic Chagas Disease (P05267) (STOP CHAGAS). Available from: https://clinicaltrials.gov/ct2/show/NCT01377480
  • Proof-of-Concept Study of E1224 to Treat Adult Patients With Chagas Disease. Available from: https://clinicaltrials.gov/ct2/show/NCT01489228
  • Chatelain E. Chagas disease drug discovery: toward a new era. J Biomol Screen 2015;20:22-35
  • Molina I, Salvador F, Sanchez-Montalva A. Posaconazole versus benznidazole for chronic Chagas’ disease. N Engl J Med 2014;371:966
  • Andrade SG, Rassi A, Magalhaes JB, et al. Specific chemotherapy of Chagas disease: a comparison between the response in patients and experimental animals inoculated with the same strains. Trans R Soc Trop Med Hyg 1992;86:624-6
  • Filardi LS, Brener Z. Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease. Trans R Soc Trop Med Hyg 1987;81:755-9
  • Murta SM, Gazzinelli RT, Brener Z, Romanha AJ. Molecular characterization of susceptible and naturally resistant strains of Trypanosoma cruzi to benznidazole and nifurtimox. Mol Biochem Parasitol 1998;93:203-14
  • Zingales B, Miles MA, Moraes CB, et al. Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity. Mem Inst Oswaldo Cruz 2014;109:828-33
  • Mejia AM, Hall BS, Taylor MC, et al. Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population. J Infect Dis 2012;206:220-8
  • Wilkinson SR, Taylor MC, Horn D, et al. A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes. Proc Natl Acad Sci U S A 2008;105:5022-7
  • Neal RA, van Bueren J. Comparative studies of drug susceptibility of five strains of Trypanosoma cruzi in vivo and in vitro. Trans R Soc Trop Med Hyg 1988;82:709-14
  • Teston AP, Monteiro WM, Reis D, et al. In vivo susceptibility to benznidazole of Trypanosoma cruzi strains from the western Brazilian Amazon. Trop Med Int Health 2013;18:85-95
  • Lewis MD, Francisco AF, Taylor MC, Kelly JM. A new experimental model for assessing drug efficacy against Trypanosoma cruzi infection based on highly sensitive in vivo imaging. J Biomol Screen 2015;20:36-43
  • Lewis MD, Fortes Francisco A, Taylor MC, et al. Bioluminescence imaging of chronic Trypanosoma cruzi infections reveals tissue-specific parasite dynamics and heart disease in the absence of locally persistent infection. Cell Microbiol 2014;16:1285-300
  • Marin-Neto JA, Rassi AJr, Avezum AJr, et al. The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease. Mem Inst Oswaldo Cruz 2009;104(Suppl 1):319-324
  • Pless M, Juranek D, Kozarsky P, et al. The epidemiology of Chagas’ disease in a hyperendemic area of Cochabamba, Bolivia: a clinical study including electrocardiography, seroreactivity to Trypanosoma cruzi, xenodiagnosis, and domiciliary triatomine distribution. Am J Trop Med Hyg 1992;47:539-46
  • Apt W, Aguilera X, Arribada A, et al. Treatment of chronic Chagas’ disease with itraconazole and allopurinol. Am J Trop Med Hyg 1998;59:133-8
  • McElroy K, Thomas T, Luciani F. Deep sequencing of evolving pathogen populations: applications, errors, and bioinformatics solutions. Microb Inform Exp 2014;4:1
  • Juliano JJ, Porter K, Mwapasa V, et al. Exposing malaria in-host diversity and estimating population diversity by capture-recapture using massively parallel pyrosequencing. Proc Natl Acad Sci USA 2010;107:20138-43
  • Manske M, Miotto O, Campino S, et al. Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature 2012;487:375-9
  • Taylor SM, Parobek CM, Aragam N, et al. Pooled deep sequencing of Plasmodium falciparum isolates: an efficient and scalable tool to quantify prevailing malaria drug-resistance genotypes. J Infect Dis 2013;208:1998-2006
  • Llewellyn MS, Messenger LA, Luquetti AO, et al. Deep sequencing of Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients. Plos Negl Trop Dis 2015;9:e0003458
  • Tibayrenc M, Miles MA. A genetic comparison between Brazilian and Bolivian zymodemes of Trypanosoma cruzi. Trans R Soc Trop Med Hyg 1983;77:76-83
  • Chapman MD, Baggaley RC, Godfrey-Fausset PF, et al. Trypanosoma cruzi from the Paraguayan Chaco: isoenzyme profiles of strains isolated at Makthlawaiya. J Protozool 1984;31:482-6
  • Povoa MM, de Souza AA, Naiff RD, et al. Chagas’ disease in the Amazon basin IV. Host records of Trypanosoma cruzi zymodemes in the states of Amazonas and Rondonia. Brazil. Ann Trop Med Parasitol 1984;78:479-87
  • Carneiro M, Chiari E, Goncalves AM, et al. Changes in the isoenzyme and kinetoplast DNA patterns of Trypanosoma cruzi strains induced by maintenance in mice. Acta Trop 1990;47:35-45
  • Romanha AJ. Heterogeneidade enzimática em Trypanosoma cruzi. PhD Thesis. 1982. UFMG; Belo Horizonte: pp 110
  • Luca D’Oro GM, Gardenal CN, Perret B, et al. Genetic structure of Trypanosoma cruzi populations from Argentina estimated from enzyme polymorphism. Parasitology 1993;107:405-10
  • Mendonca MB, Nehme NS, Santos SS, et al. Two main clusters within Trypanosoma cruzi zymodeme 3 are defined by distinct regions of the ribosomal RNA cistron. Parasitology 2002;124:177-84
  • Kawashita SY, Sanson GF, Fernandes O, et al. Maximum-likelihood divergence date estimates based on rRNA gene sequences suggest two scenarios of Trypanosoma cruzi intraspecific evolution. Mol Biol Evol 2001;18:2250-9
  • Augusto-Pinto L, Teixeira SM, Pena SD, Machado CR. Single-nucleotide polymorphisms of the Trypanosoma cruzi MSH2 gene support the existence of three phylogenetic lineages presenting differences in mismatch-repair efficiency. Genetics 2003;164:117-26
  • Nunes LR, de Carvalho MR, Buck GA. Trypanosoma cruzi strains partition into two groups based on the structure and function of the spliced leader RNA and rRNA gene promoters. Mol Biochem Parasitol 1997;86:211-24
  • Pennington PM, Paiz C, Grajeda LM, Cordon-Rosales C. Concurrent detection of Trypanosoma cruzi lineages I and II in domestic Triatoma dimidiata from Guatemala. Am J Trop Med Hyg 2009;80:239-41
  • Higo H, Miura S, Horio M, et al. Genotypic variation among lineages of Trypanosoma cruzi and its geographic aspects. Parasitol Int 2004;53:337-44
  • Zafra G, Mantilla JC, Valadares HM, et al. Evidence of Trypanosoma cruzi II infection in Colombian chagasic patients. Parasitol Res 2008;103:731-4
  • Martins LP, Marcili A, Castanho RE, et al. Rural Triatoma rubrovaria from southern Brazil harbors Trypanosoma cruzi of lineage IIc. Am J Trop Med Hyg 2008;79:427-34
  • Corrales RM, Mora MC, Negrette OS, et al. Congenital Chagas disease involves Trypanosoma cruzi sub-lineage IId in the northwestern province of Salta, Argentina. Infect Genet Evol 2009;9:278-82
  • Ramos-Ligonio A, Torres-Montero J, Lopez-Monteon A, Dumonteil E. Extensive diversity of Trypanosoma cruzi discrete typing units circulating in Triatoma dimidiata from central Veracruz, Mexico. Infect Genet Evol 2012;12:1341-3
  • Ready PD, Miles MA. Delimitation of Trypanosoma cruzi zymodemes by numerical taxonomy. Trans R Soc Trop Med Hyg 1980;74:238-42
  • Sturm NR, Degrave W, Morel C, Simpson L. Sensitive detection and schizodeme classification of Trypanosoma cruzi cells by amplification of kinetoplast minicircle DNA sequences: use in diagnosis of Chagas’ disease. Mol Biochem Parasitol 1989;33:205-14
  • Britto C, Cardosa MA, Ravel C, et al. Trypanosoma cruzi: parasite detection and strain discrimination in chronic chagasic patients from northeastern Brazil using PCR amplification of kinetoplast DNA and nonradioactive probes. Exp Parasitol 1995;81:462-71
  • Henriksson J, Porcel BM, Rydaker M, et al. Chromosome-specific markers reveal conserved linkage groups in spite of extensive chromosomal size variation in Trypanosoma cruzi. Mol Biochem Parasitol 1995;73:63-74
  • Pena SD, Barreto G, Vago AR, et al. Sequence-specific ‘gene signatures’ can be obtained by PCR with single specific primers at low stringency. Proc Natl Acad Sci U S A 1994;91:1946-9
  • Vago AR, Macedo AM, Adad SJ, et al. PCR detection of Trypanosoma cruzi DNA in esophageal tissues of patients with chronic Chagas disease. Lancet 1996;348:891-2
  • Vago AR, Macedo AM, Oliveira RP, et al. Kinetoplast DNA signatures of Trypanosoma cruzi strains obtained directly from infected tissues. Am J Pathol 1996;149:2153-9
  • De Leon MP, Yanagi T, Kikuchi M, et al. Characterisation of Trypanosoma cruzi populations by DNA polyrmophism of the cruzipain gene detected by single-stranded DNA conformation polymorphism (SSCP) and direct sequencing. Int J Parasitol 1998;28:1867-74
  • Vazquez MP, Beldjord C, Lorenzi H, et al. Detection of polymorphism in the Trypanosoma cruzi TcP2 beta gene family by single strand conformational analysis (SSCA). Gene 1996;180:43-8
  • Rozas M, De Doncker S, Adaui V, et al. Multilocus polymerase chain reaction restriction fragment-length polymorphism genotyping of Trypanosoma cruzi (Chagas disease): taxonomic and clinical applications. J Infect Dis 2007;195:1381-8
  • Lauthier JJ, Tomasini N, Barnabe C, et al. Candidate targets for Multilocus Sequence Typing of Trypanosoma cruzi: validation using parasite stocks from the Chaco Region and a set of reference strains. Infect Genet Evol 2012;12:350-8
  • Messenger LA, Llewellyn MS, Bhattacharyya T, et al. Multiple mitochondrial introgression events and heteroplasmy in trypanosoma cruzi revealed by maxicircle MLST and next generation sequencing. Plos Negl Trop Dis 2012;6:e1584
  • Carranza JC, Valadares HM, D’Avila DA, et al. Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil. Int J Parasitol 2009;39:963-73
  • Hamilton PB, Lewis MD, Cruickshank C, et al. Identification and lineage genotyping of South American trypanosomes using fluorescent fragment length barcoding. Infect Genet Evol 2011;11:44-51
  • Higuera SL, Guhl F, Ramirez JD. Identification of Trypanosoma cruzi discrete typing units (DTUs) through the implementation of a high-resolution melting (HRM) genotyping assay. Parasit Vectors 2013;6:112
  • Macedo AM, Pimenta JR, Aguiar RS, et al. Usefulness of microsatellite typing in population genetic studies of Trypanosoma cruzi. Mem Inst Oswaldo Cruz 2001;96:407-13
  • Storino R, Milei J. Enfermedad de Chagas Buenos Aires, Argentina: Mosby-Doyma Argentina. 1994
  • Rezende JM. Clínica: manifestações digestivas, In: Trypanossoma Cruzi e Doença de Chagas. Rio de Janeiro, Brazil: Guanabara Koogan; 1979
  • Ben Abderrazak S, Guerrini F, Mathieu-Daude F, et al. Isozyme electrophoresis for parasite characterization.In: Methods in Molecular Biology, Protocols in Molecular Parasitology. Totowa, NJ: Humana Press; 1993
  • Tibayrenc M, Le Ray D. General classification of the isoenzymic strains of Trypanosoma (Schizotrypanum) cruzi and comparison with T.(S.) c. marinkellei and T. (Herpetosoma) rangeli. Ann Soc Belge Med Trop 1984;64:239-48
  • Acosta N, Samudio M, Lopez E, et al. Isoenzyme profiles of Trypanosoma cruzi stocks from different areas of Paraguay. Mem Inst Oswaldo Cruz 2001;96:527-33
  • Veas F, Breniere SF, Cuny G, et al. General procedure to construct highly specific kDNA probes for clones of Trypanosoma cruzi for sensitive detection by polymerase chain reaction. Cell Mol Biol 1991;37:73-84
  • Burgos JM, Begher SB, Freitas JM, et al. Molecular diagnosis and typing of Trypanosoma cruzi populations and lineages in cerebral Chagas disease in a patient with AIDS. Am J Trop Med Hyg 2005;73:1016-18
  • Bisio M, Cura C, Duffy T, et al. Trypanosoma cruzi discrete typing units in Chagas disease patients with HIV co-infection. Rev Biomed 2009;20:166-78
  • Cura CI, Lattes R, Nagel C, et al. Early molecular diagnosis of acute Chagas disease after transplantation with organs from Trypanosoma cruzi-infected donors. Am J Transplant 2013;13:3253-61
  • Lages-Silva E, Ramirez LE, Silva-Vergara ML, Chiari E. Chagasic meningoencephalitis in a patient with acquired immunodeficiency syndrome: diagnosis, follow-up, and genetic characterization of Trypanosoma cruzi. Clin Infect Dis 2002;34:118-23
  • Perez-Ramirez L, Barnabé C, Sartori AM, et al. Clinical analysis and parasite genetic diversity in human immunodeficiency virus/Chagas’ disease coinfections in Brazil. Am J Trop Med Hyg 1999;61:198-206
  • Hernandez C, Cucunuba Z, Parra E, et al. Chagas disease (Trypanosoma cruzi) and HIV co-infection in Colombia. Int J Infect Dis 2014;26:146-8
  • Burgos JM, Altcheh J, Petrucelli N, et al. Molecular diagnosis and treatment monitoring of congenital transmission of Trypanosoma cruzi to twins of a triplet delivery. Diagn Microbiol Infect Dis 2009;65:58-61
  • Bittencourt AL, Mota E. Isoenzyme characterization of Trypanosoma cruzi from congenital cases of Chagas’ disease. Ann Trop Med Parasitol 1985;79:393-6
  • Bosseno MF, Torrico F, Telleria J, et al. Reaccion de polimerasa en cadena: deteccion y caracterizacion de cepas de Trypanosoma cruzi en niños chagásicos. Medicina (B Aires) 1995;55:277-8
  • Garcia A, Ortiz S, Iribarren C, et al. Congenital co-infection with different Trypanosoma cruzi lineages. Parasitol Int 2014;63:138-9
  • Murcia L, Carrilero B, Munoz-Davila MJ, et al. Risk factors and primary prevention of congenital Chagas disease in a nonendemic country. Clin Infect Dis 2013;56:496-502
  • Steindel M, Toma HK, Ishida MM, et al. Biological and isoenzymatic characterization of Trypanosoma cruzi strains isolated from sylvatic reservoirs and vectors from the State of Santa Catarina, Southern Brazil. Acta Trop 1995;60:167-77
  • Fernandes O, Santos SS, Cupolillo E, et al. A mini-exon multiplex polymerase chain reaction to distinguish the major groups of Trypanosoma cruzi and T. rangeli in the Brazilian Amazon. Trans R Soc Trop Med Hyg 2001;95:97-9
  • Maia da Silva F, Noyes H, Campaner M, et al. Phylogeny, taxonomy and grouping of Trypanosoma rangeli isolates from man, triatomines and sylvatic mammals from widespread geographical origin based on SSU and ITS ribosomal sequences. Parasitology 2004;129:549-61