Abstract
Introduction. Trypanosoma cruzi is the pro- tozoan hemoflagellate that causes Chagas dis- ease, an endemic illness in Latin America that is highly incapacitating and incurable. The par- asite strains have great intraspecific variability, being classified into seven DTUs (from TcI to TcVI and Tcbat). In addition to their different geographical distribution, T. cruzi strains show biological, biochemical, molecular and anti- genic diversity, which is related to the develop- ment of the different clinical symptoms of the disease, the efficiency of diagnosis and treat- ment response. Serodiagnosis tests show wide variation in their sensitivity and specificity, and so far, it doesn't exist a standard gold test for a completely reliable diagnosis. Objective. To review the advances made in the search for useful antigens for serodiagnosis of Chagas disease. Materials and methods. We per- formed a qualitative systematic review of re- ports related to serodiagnosis of T. cruzi infec- tion found in PubMed. Results. Conventional serodiagnosis with complete parasite antigens is sensitive but does not have high specificity. Thus, unconventional tests with recombinant antigens or synthetic peptides that increase specificity are also used. Different approaches have allowed the identification of molecules with potential diagnostic, showing that cock- tails of recombinant antigen, mixtures of syn- thetic peptides or multiepitope antigens are necessary for a better sensitivity and specifici- ty of the tests and infection detection with any T. cruzi DTU. Conclusions. Even though several antigens with potential use for diagnosis have been identified, efforts continue to identify new and better antigens. Recent advances in large-scale proteomics linked with immunoas- says and immunogenomics offer an opportuni- ty in the search not only for biomarkers for di- agnosis, but also for the treatment and timely prognosis of Chagas disease.
References
Arnal, A., Waleckx, E., Rico-Chavez, O., Herrera, C., & Dumonteil, E. (2019). Estimating the current burden of Chagas disease in Mexico: A systematic review and meta-analysis of epidemiological surveys from 2006 to 2017. PLoS Neglected Tropical Diseases, 13(4), e0006859. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30964871. doi:10.1371/journal.pntd.0006859
Avila, H. A., Pereira, J. B., Thiemann, O., De Paiva, E., DeGrave, W., Morel, C. M., & Simpson, L. (1993). Detection of Trypanosoma cruzi in blood specimens of chronic chagasic patients by polymerase chain reaction amplification of kinetoplast minicircle DNA: comparison with serology and xenodiagnosis. Journal of Clinical Microbiology, 31(9), 2421-2426. Retrieved fromhttp://www.ncbi.nlm.nih.gov/pubmed/8408566.
Balouz, V., Melli, L. J., Volcovich, R., Moscatelli, G., Moroni, S., Gonzalez, N., Altcheh, J. (2017). The Trypomastigote Small Surface Antigen from Trypanosoma cruzi Improves Treatment Evaluation and Diagnosis in Pediatric Chagas Disease. Journal of Clinical Microbiology, 55(12), 3444-3453. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28978686. doi:10.1128/JCM.01317-17
Bhattacharyya, T., Brooks, J., Yeo, M., Carrasco, H. J., Lewis, M. D., Llewellyn, M. S., & Miles, M. A. (2010). Analysis of molecular diversity of the Trypanosoma cruzi trypomastigote small surface antigen reveals novel epitopes, evidence of positive selection and potential implications for lineage-specific serology. International Journal for Parasitology, 40(8), 921-928. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20097201. doi:10.1016/j.ijpara.2010.01.002
Bivona, A. E., Sanchez Alberti, A., Matos, M. N., Cerny, N., Cardoso, A. C., Morales, C., Malchiodi, E. L. (2018). Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine. PLoS Neglected Tropical Diseases, 12(3), e0006384. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29601585. doi:10.1371/journal.pntd.0006384
Bosseno, M. F., Barnabe, C., Magallon Gastelum, E., Lozano Kasten, F., Ramsey, J., Espinoza, B., & Breniere, S. F. (2002). Predominance of Trypanosoma cruzi lineage I in Mexico. Journal of Clinical Microbiology, 40(2), 627-632. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11825982.
Bosseno, M. F., Barnabe, C., Sierra, M. J., Kengne, P., Guerrero, S., Lozano, F., Breniere, S. F. (2009). Wild ecotopes and food habits of Triatoma longipennis infected by Trypanosoma cruzi lineages I and II in Mexico. American Journal of Tropical Medicine and Hygiene, 80(6), 988-991. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19478263.
Breniere, S. F., Waleckx, E., & Barnabe, C. (2016). Over Six Thousand Trypanosoma cruzi Strains Classified into Discrete Typing Units (DTUs): Attempt at an Inventory. PLoS Neglected Tropical Diseases, 10(8), e0004792. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27571035. doi:10.1371/journal.pntd.0004792
Briones, M. R., Souto, R. P., Stolf, B. S., & Zingales, B. (1999). The evolution of two Trypanosoma cruzi subgroups inferred from rRNA genes can be correlated with the interchange of American mammalian faunas in the Cenozoic and has implications to pathogenicity and host specificity. Molecular and Biochemical Parasitology, 104(2), 219-232. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10593177.
Burgos, J. M., Begher, S., Silva, H. M., Bisio, M., Duffy, T., Levin, M. J., Schijman, A. G. (2008). Molecular identification of Trypanosoma cruzi I tropism for central nervous system in Chagas reactivation due to AIDS. American Journal of Tropical Medicine and Hygiene, 78(2), 294-297. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18256432.
Caeiro, L. D., Alba-Soto, C. D., Rizzi, M., Solana, M. E., Rodriguez, G., Chidichimo, A. M., Tekiel, V. (2018). The protein family TcTASV-C is a novel Trypanosoma cruzi virulence factor secreted in extracellular vesicles by trypomastigotes and highly expressed in bloodstream forms. PLoS Neglected Tropical Diseases, 12(5), e0006475. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29727453. doi:10.1371/journal.pntd.0006475
CENAPRECE. (2015). Manual de diagnóstico y tratamiento de la enfermedad de Chagas. Retrieved from https://www.gob.mx/cms/uploads/attachment/file/235962/ManualDX_TxEnfermedadCHAGAS2015.pdf
Chippaux, J. P., Santalla, J. A., Postigo, J. R., Romero, M., Salas Clavijo, N. A., Schneider, D., & Brutus, L. (2009). Sensitivity and specificity of Chagas Stat-Pak test in Bolivia. Tropical Medicine and International Health, 14(7), 732-735. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19392737. doi:10.1111/j.1365-3156.2009.02288.x
Coura, J. R. (2007). Chagas disease: what is known and what is needed—a background article. Memorias do Instituto Oswaldo Cruz, 102 Suppl 1, 113-122. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17992371.
Coura, J. R., & Borges-Pereira, J. (2010). Chagas disease: 100 years after its discovery. A systemic review. Acta Tropica, 115(1-2), 5-13. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20382097. doi:10.1016/j.actatropica.2010.03.008
Cruz-Reyes, A., & Pickering-Lopez, J. M. (2006). Chagas disease in Mexico: an analysis of geographical distribution during the past 76 years--a review. Memorias do Instituto Oswaldo Cruz, 101(4), 345-354. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16951802.
da Silveira, J. F., Umezawa, E. S., & Luquetti, A. O. (2001). Chagas disease: recombinant Trypanosoma cruzi antigens for serological diagnosis. Trends in Parasitology, 17(6), 286-291. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11378036.
Del-Rei, R. P., Leony, L. M., Celedon, P. A. F., Zanchin, N. I. T., Reis, M. G. D., Gomes, Y. M., Santos, F. L. N. (2019). Detection of anti-Trypanosoma cruzi antibodies by chimeric antigens in chronic Chagas disease-individuals from endemic South American countries. PLoS One, 14(4), e0215623. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30998741. doi:10.1371/journal.pone.0215623
Di Noia, J. M., Buscaglia, C. A., De Marchi, C. R., Almeida, I. C., & Frasch, A. C. (2002). A Trypanosoma cruzi small surface molecule provides the first immunological evidence that Chagas' disease is due to a single parasite lineage. Journal of Experimental Medicine, 195(4), 401-413. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11854354.
Diez, C. N., Manattini, S., Zanuttini, J. C., Bottasso, O., & Marcipar, I. (2008). The value of molecular studies for the diagnosis of congenital Chagas disease in northeastern Argentina. American Journal of Tropical Medicine and Hygiene, 78(4), 624-627. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18385359.
Dorn, P. L., McClure, A. G., Gallaspy, M. D., Waleckx, E., Woods, A. S., Monroy, M. C., & Stevens, L. (2017). The diversity of the Chagas parasite, Trypanosoma cruzi, infecting the main Central American vector, Triatoma dimidiata, from Mexico to Colombia. PLoS Neglected Tropical Diseases, 11(9), e0005878. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28957315. doi:10.1371/journal.pntd.0005878
Dumonteil, E. (1999). Update on Chagas' disease in Mexico. Salud Publica de México, 41(4), 322-327. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10624144.
Duthie, M. S., Guderian, J. A., Vallur, A. C., Misquith, A., Liang, H., Mohamath, R., Reed, S. G. (2016). Multi-epitope proteins for improved serological detection of Trypanosoma cruzi infection and Chagas Disease. Diagnostic Microbiology and Infectious Disease, 84(3), 191-196. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26658314. doi:10.1016/j.diagmicrobio.2015.11.006
Egui, A., Thomas, M. C., Fernandez-Villegas, A., Perez-Anton, E., Gomez, I., Carrilero, B., Lopez, M. C. (2019). A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi Infection. Antimicrobial Agents and Chemotherapy, 63(10). Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/31358581. doi:10.1128/AAC.02436-18
El-Sayed, N. M., Myler, P. J., Bartholomeu, D. C., Nilsson, D., Aggarwal, G., Tran, A. N., Andersson, B. (2005). The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science, 309(5733), 409-415. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16020725. doi:10.1126/science.1112631
Elisei, R. M. T., Matos, C. S., Carvalho, A., Chaves, A. T., Medeiros, F. A. C., Barbosa, R., Menezes-Souza, D. (2018). Immunogenomic screening approach to identify new antigens for the serological diagnosis of chronic Chagas' disease. Applied Microbiology and Biotechnology. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/29736822. doi:10.1007/s00253-018-8992-7
Espinoza Gutierrez, B., & Manning Cela, R. G. (2008). An overview of mammalian cell infection by Trypanosoma cruzi: Cellular and molecular basis. In L. I. Terrazas (Ed.), Advances in the immunobiology of parasitic disases. Kerala, India. : Research Signpost.
Floridia-Yapur, N., Monje-Rumi, M., Ragone, P., Lauthier, J. J., Tomasini, N., Alberti D'Amato, A., Tekiel, V. (2019). TcTASV Antigens of Trypanosoma cruzi: Utility for Diagnosis and High Accuracy as Biomarkers of Treatment Efficacy in Pediatric Patients. American Journal of Tropical Medicine and Hygiene, 101(5), 1135-1138. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/31516110. doi:10.4269/ajtmh.18-0936
Freitas, J. M., Lages-Silva, E., Crema, E., Pena, S. D., & Macedo, A. M. (2005). Real time PCR strategy for the identification of major lineages of Trypanosoma cruzi directly in chronically infected human tissues. International Journal for Parasitology, 35(4), 411-417. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15777917. doi:10.1016/j.ijpara.2004.10.023
Galvão, C., Carcavallo, R., Rocha-Da Silva, D., & Jurberg, J. (2003). A checklist of the current valid species of the subfamily Triatiominae Jeannel, 1919 (Hemiptera: Reduviidae) and their geographical distribution, with nomenclatural and taxonomic notes. Zootaxa, 202, 1-36.
Gomes, Y. M., Lorena, V. M., & Luquetti, A. O. (2009). Diagnosis of Chagas disease: what has been achieved? What remains to be done with regard to diagnosis and follow up studies? Memorias do Instituto Oswaldo Cruz, 104 Suppl 1, 115-121. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19753466.
Gomez-Hernandez, C., Rezende-Oliveira, K., Nascentes, G. A., Batista, L. R., Kappel, H. B., Martinez-Ibarra, J. A., Ramirez, L. E. (2011). Molecular characterization of Trypanosoma cruzi Mexican strains and their behavior in the mouse experimental model. Revista da Sociedade Brasileira de Medicina Tropical, 44(6), 684-690. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22094706.
Guzman-Bracho, C. (2001). Epidemiology of Chagas disease in Mexico: an update. Trends in Parasitology, 17(8), 372-376. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11685897.
Guzman-Gomez, D., Lopez-Monteon, A., de la Soledad Lagunes-Castro, M., Alvarez-Martinez, C., Hernandez-Lutzon, M. J., Dumonteil, E., & Ramos-Ligonio, A. (2015). Highly discordant serology against Trypanosoma cruzi in central Veracruz, Mexico: role of the antigen used for diagnostic. Parasites & Vectors, 8, 466. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26384317. doi:10.1186/s13071-015-1072-2
Henriksson, J., Dujardin, J. C., Barnabe, C., Brisse, S., Timperman, G., Venegas, J., Solari, A. (2002). Chromosomal size variation in Trypanosoma cruzi is mainly progressive and is evolutionarily informative. Parasitology, 124(Pt 3), 277-286. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11922429.
Ibanez-Cervantes, G., Martinez-Ibarra, A., Nogueda-Torres, B., Lopez-Orduna, E., Alonso, A. L., Perea, C., Leon-Avila, G. (2013). Identification by Q-PCR of Trypanosoma cruzi lineage and determination of blood meal sources in triatomine gut samples in Mexico. Parasitology International, 62(1), 36-43. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22995149. doi:10.1016/j.parint.2012.09.003
Justi, S. A., & Galvao, C. (2017). The Evolutionary Origin of Diversity in Chagas Disease Vectors. Trends in Parasitology, 33(1), 42-52. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27986547. doi:10.1016/j.pt.2016.11.002
Kim, Y. H., Yang, Z., Lee, J., Ahn, H. J., Chong, C. K., Maricondi, W., Nam, H. W. (2019). Detection of Human Anti-Trypanosoma cruzi Antibody with Recombinant Fragmented Ribosomal P Protein. Korean Journal of Parasitology, 57(4), 435-437. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/31533412. doi:10.3347/kjp.2019.57.4.435
Lages-Silva, E., Ramirez, L. E., Pedrosa, A. L., Crema, E., da Cunha Galvao, L. M., Pena, S. D., Chiari, E. (2006). Variability of kinetoplast DNA gene signatures of Trypanosoma cruzi II strains from patients with different clinical forms of Chagas' disease in Brazil. Journal of Clinical Microbiology, 44(6), 2167-2171. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16757616. doi:10.1128/JCM.02124-05
Lee, B. Y., Bacon, K. M., Bottazzi, M. E., & Hotez, P. J. (2013). Global economic burden of Chagas disease: a computational simulation model. The Lancet Infectious Diseases, 13(4), 342-348. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23395248. doi:10.1016/S1473-3099(13)70002-1
Lewis, M. D., Llewellyn, M. S., Gaunt, M. W., Yeo, M., Carrasco, H. J., & Miles, M. A. (2009). Flow cytometric analysis and microsatellite genotyping reveal extensive DNA content variation in Trypanosoma cruzi populations and expose contrasts between natural and experimental hybrids. International Journal for Parasitology, 39(12), 1305-1317. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19393242. doi:10.1016/j.ijpara.2009.04.001
Luquetti, Ponce, C., Ponce, E., Esfandiari, J., Schijman, A., Revollo, S., Franco da Silveira, J. (2003). Chagas' disease diagnosis: a multicentric evaluation of Chagas Stat-Pak, a rapid immunochromatographic assay with recombinant proteins of Trypanosoma cruzi. Diagnostic Microbiology and Infectious Disease, 46(4), 265-271. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/12944018. doi:10.1016/s0732-8893(03)00051-8
Luquetti, A., Miles, M., Rassi, A., de Rezende, J., de Souza, A., Póvoa, M., & Rodrigues, I. (1986). Trypanosoma cruzi: zimodemes associated with acute and chronic Chagas’ disease in central Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene, 80, 462-470.
Marcipar, I. S., & Lagier, C. M. (2012). Advances in Serological Diagnosis of Chagas’ Disease by Using Recombinant Proteins. In A. J. Rodriguez-Morales (Ed.), Current Topics in Tropical Medicine (pp. 1-28): InTechOpen.
Mendes, T. A., Reis Cunha, J. L., de Almeida Lourdes, R., Rodrigues Luiz, G. F., Lemos, L. D., dos Santos, A. R., Bartholomeu, D. C. (2013). Identification of strain-specific B-cell epitopes in Trypanosoma cruzi using genome-scale epitope prediction and high-throughput immunoscreening with peptide arrays. PLoS Neglected Tropical Diseases, 7(10), e2524. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24205430. doi:10.1371/journal.pntd.0002524
Montalvao, F., Nascimento, D. O., Nunes, M. P., Koeller, C. M., Morrot, A., Lery, L. M. S., Freire-de-Lima, C. G. (2018). Antibody Repertoires Identify beta-Tubulin as a Host Protective Parasite Antigen in Mice Infected With Trypanosoma cruzi. Frontiers in Immunology, 9, 671. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29706955. doi:10.3389/fimmu.2018.00671
OPS-OMS. (2018). Guía para el diagnóstico y el tratamiento de la enfermedad de Chagas. Retrieved from https://iris.paho.org/bitstream/handle/10665.2/49653/9789275320433_spa.pdf?sequence=9&isAllowed=y
OPS. (2020). Enfermedad de Chagas. Retrieved from https://www.paho.org/es/temas/enfermedad-chagas
Pech-May, A., Mazariegos-Hidalgo, C. J., Izeta-Alberdi, A., Lopez-Cancino, S. A., Tun-Ku, E., De la Cruz-Felix, K., Ramsey, J. M. (2019). Genetic variation and phylogeography of the Triatoma dimidiata complex evidence a potential center of origin and recent divergence of haplogroups having differential Trypanosoma cruzi and DTU infections. PLoS Neglected Tropical Diseases, 13(1), e0007044. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30689662. doi:10.1371/journal.pntd.0007044
Pedroso, A., Cupolillo, E., & Zingales, B. (2003). Evaluation of Trypanosoma cruzi hybrid stocks based on chromosomal size variation. Molecular and Biochemical Parasitology, 129(1), 79-90. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12798509.
Perez-Fuentes, R., Sanchez-Guillen, M. C., Gonzalez-Alvarez, C., Monteon, V. M., Reyes, P. A., & Rosales-Encina, J. L. (1998). Humoral nitric oxide levels and antibody immune response of symptomatic and indeterminate Chagas' disease patients to commercial and autochthonous Trypanosoma cruzi antigen. The American Journal of Tropical Medicine and Hygiene, 58(6), 715-720. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9660451.
Peverengo, L. M., Garcia, V., Rodeles, L. M., Mendicino, D., Vicco, M., Lagier, C., Marcipar, I. (2018). Development and assessment of an improved recombinant multiepitope antigen-based immunoassay to diagnose chronic Chagas disease. Parasitology, 145(12), 1594-1599. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29587896. doi:10.1017/S0031182018000458
Pitarch, A., Nombela, C., & Gil, C. (2010). [Proteomics, a new challenge for clinical microbiology]. Enfermedades Infecciosas y Microbiología Clínica, 28(8), 489-491. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20888998. doi:10.1016/j.eimc.2010.08.001
Ponce, C., Ponce, E., Vinelli, E., Montoya, A., de Aguilar, V., Gonzalez, A., da Silveira, J. F. (2005). Validation of a rapid and reliable test for diagnosis of chagas' disease by detection of Trypanosoma cruzi-specific antibodies in blood of donors and patients in Central America. Journal of Clinical Microbiology, 43(10), 5065-5068. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16207963. doi:10.1128/JCM.43.10.5065-5068.2005
Portillo, S., Zepeda, B. G., Iniguez, E., Olivas, J. J., Karimi, N. H., Moreira, O. C., Almeida, I. C. (2019). A prophylactic alpha-Gal-based glycovaccine effectively protects against murine acute Chagas disease. NPJ Vaccines, 4, 13. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30911415. doi:10.1038/s41541-019-0107-7
Ramos-Ligonio, A., Torres-Montero, J., Lopez-Monteon, A., & Dumonteil, E. (2012). Extensive diversity of Trypanosoma cruzi discrete typing units circulating in Triatoma dimidiata from central Veracruz, Mexico. Infection, Genetics and Evolution, 12(7), 1341-1343. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22569098. doi:10.1016/j.meegid.2012.04.024
Ramsey, J. M., Ordonez, R., Cruz-Celis, A., Alvear, A. L., Chavez, V., Lopez, R., Carrillo, S. (2000). Distribution of domestic triatominae and stratification of Chagas Disease transmission in Oaxaca, Mexico. Medical and Veterinary Entomology, 14(1), 19-30. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10759308.
Ramsey, J. M., Peterson, A. T., Carmona-Castro, O., Moo-Llanes, D. A., Nakazawa, Y., Butrick, M., Ibarra-Cerdena, C. N. (2015). Atlas of Mexican Triatominae (Reduviidae: Hemiptera) and vector transmission of Chagas disease. Memorias do Instituto Oswaldo Cruz, 110(3), 339-352. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25993505. doi:10.1590/0074-02760140404
Ramsey, J. M., & Schofield, C. J. (2003). Control of Chagas disease vectors. Salud Publica de México, 5(2), 123-128. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12736992.
Rassi, A., Jr., Rassi, A., & Little, W. C. (2000). Chagas' heart disease. Clinical Cardiology, 23(12), 883-889. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11129673.
Rassi, A., Jr., Rassi, A., & Marin-Neto, J. A. (2010). Chagas disease. Lancet, 375(9723), 1388-1402. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20399979. doi:10.1016/S0140-6736(10)60061-X
Reis-Cunha, J. L., Mendes, T. A., de Almeida Lourdes, R., Ribeiro, D. R., Machado-de-Avila, R. A., de Oliveira Tavares, M., Bartholomeu, D. C. (2014). Genome-wide screening and identification of new Trypanosoma cruzi antigens with potential application for chronic Chagas disease diagnosis. PLoS One, 9(9), e106304. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25225853. doi:10.1371/journal.pone.0106304
Ruiz-Sanchez, R., Leon, M. P., Matta, V., Reyes, P. A., Lopez, R., Jay, D., & Monteon, V. M. (2005). Trypanosoma cruzi isolates from Mexican and Guatemalan acute and chronic chagasic cardiopathy patients belong to Trypanosoma cruzi I. Memorias do Instituto Oswaldo Cruz, 100(3), 281-283. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16113869. doi:/S0074-02762005000300012
Salazar Schettino, P. M., Bucio Torres, M. I., Rojo Mdina, J., & Manuel Valencia, Y. V. (2019). Manual de procedimientos para la Enfermedad de Chagas en México. Retrieved from https://www.gob.mx/cms/uploads/attachment/file/447946/Manual_de_Procedimientos_para_la_Enfermedad_de_Chagas_en_Mexico.pdf
Sanchez-Guillen, M. C., Lopez-Colombo, A., Ordonez-Toquero, G., Gomez-Albino, I., Ramos-Jimenez, J., Torres-Rasgado, E., Perez-Fuentes, R. (2006). Clinical forms of Trypanosoma cruzi infected individuals in the chronic phase of Chagas disease in Puebla, Mexico. Memorias do Instituto Oswaldo Cruz, 101(7), 733-740. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17160280.
Santos, F. L., Celedon, P. A., Zanchin, N. I., de Souza, W. V., da Silva, E. D., Foti, L., Gomes, Y. M. (2017). Accuracy of chimeric proteins in the serological diagnosis of chronic chagas disease - a Phase II study. PLoS Neglected Tropical Diseases, 11(3), e0005433. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28273127. doi:10.1371/journal.pntd.0005433
Souza, R. T., Lima, F. M., Barros, R. M., Cortez, D. R., Santos, M. F., Cordero, E. M., da Silveira, J. F. (2011). Genome size, karyotype polymorphism and chromosomal evolution in Trypanosoma cruzi. PLoS One, 6(8), e23042. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21857989. doi:10.1371/journal.pone.0023042
Thomas, M. C., Fernandez-Villegas, A., Carrilero, B., Maranon, C., Saura, D., Noya, O., Lopez, M. C. (2012). Characterization of an immunodominant antigenic epitope from Trypanosoma cruzi as a biomarker of chronic Chagas' disease pathology. Clinical and Vaccine Immunology, 19(2), 167-173. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22155766. doi:10.1128/CVI.05566-11
Umezawa, E. S., Bastos, S. F., Coura, J. R., Levin, M. J., Gonzalez, A., Rangel-Aldao, R., da Silveira, J. F. (2003). An improved serodiagnostic test for Chagas' disease employing a mixture of Trypanosoma cruzi recombinant antigens. Transfusion, 43(1), 91-97. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/12519436. doi:10.1046/j.1537-2995.2003.00279.x
Vargas, N., Pedroso, A., & Zingales, B. (2004). Chromosomal polymorphism, gene synteny and genome size in T. cruzi I and T. cruzi II groups. Molecular and Biochemical Parasitology, 138(1), 131-141. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15500924. doi:10.1016/j.molbiopara.2004.08.005
Verani, J. R., Seitz, A., Gilman, R. H., LaFuente, C., Galdos-Cardenas, G., Kawai, V., Bern, C. (2009). Geographic variation in the sensitivity of recombinant antigen-based rapid tests for chronic Trypanosoma cruzi infection. The American Journal of Tropical Medicine and Hygiene, 80(3), 410-415. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19270291.
WHO. (2007). World Health Statistics. World Health Organization, 2, 21-31.
WHO. (2020). La enfermedad de Chagas (tripanosomiasis americana). Retrieved from https://www.who.int/es/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)
Zingales, B. (2018). Trypanosoma cruzi genetic diversity: Something new for something known about Chagas disease manifestations, serodiagnosis and drug sensitivity. Acta Tropica, 184, 38-52. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28941731. doi:10.1016/j.actatropica.2017.09.017
Zingales, B., Miles, M. A., Campbell, D. A., Tibayrenc, M., Macedo, A. M., Teixeira, M. M., Sturm, N. R. (2012). The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infection, Genetics and Evolution, 12(2), 240-253. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22226704. doi:10.1016/j.meegid.2011.12.009