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Differential tissue distribution of discrete typing units after drug combination therapy in experimental Trypanosoma cruzi mixed infection

Published online by Cambridge University Press:  21 July 2021

Mariana Strauss ,
M. Silvina Lo Presti Open the ORCID record for M. Silvina Lo Presti [Opens in a new window] ,
Juan C. Ramírez ,
P. Carolina Bazán ,
Daniela A. Velázquez López ,
Alejandra L. Báez ,
Patricia A. Paglini ,
Alejandro G. Schijman  and
Héctor W. Rivarola
Mariana Strauss*
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
M. Silvina Lo Presti*
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Juan C. Ramírez
Affiliation:
Laboratorio de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina
P. Carolina Bazán
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Daniela A. Velázquez López
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Alejandra L. Báez
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Patricia A. Paglini
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Alejandro G. Schijman
Affiliation:
Laboratorio de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina
Héctor W. Rivarola
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
*
Author for correspondence: Mariana Strauss, E-mail: marianastr86@gmail.com, M. Silvina Lo Presti, E-mail: silvinalopresti@unc.edu.ar
Author for correspondence: Mariana Strauss, E-mail: marianastr86@gmail.com, M. Silvina Lo Presti, E-mail: silvinalopresti@unc.edu.ar
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Abstract

The aim of the present work was to evaluate the distribution of the different clones of the parasite prevailing after treatment with benznidazole (BZ) and clomipramine (CLO), in mice infected with Trypanosoma cruzi, Casibla isolate which consists of a mixture of two discrete typing units (DTUs). Albino Swiss mice were infected and treated with high and low concentrations of BZ (100 or 6.25 mg/kg), CLO (5 or 1.25 mg/kg), or the combination of both low doses (BZ6.25 + CLO1.25), during the acute phase of experimental infection. Treatment efficacy was evaluated by comparing parasitaemia, survival and tissular parasite presence. For DTUs genotyping, blood, skeletal and cardiac muscle samples were analysed by multiplex quantitative polymerase chain reaction. The combined treatment had similar outcomes to BZ6.25; BZ100 was the most effective treatment, but it failed to reach parasite clearance and produced greater histological alterations. Non-treated mice and the ones treated with monotherapies showed both DTUs while BZ6.25 + CLO1.25 treated mice showed only TcVI parasites in all the tissues studied. These findings suggest that the treatment may modify the distribution of infecting DTUs in host tissues. Coinfection with T. cruzi clones belonging to different DTUs reveals a complex scenario for the treatment of Chagas disease and search for new therapies.

Keywords

Benznidazoleclomipramineclonal histotropismdiscrete typing unitsexperimental infection modelTrypanosoma cruzi
Type
Research Article
Information
Parasitology , Volume 148 , Issue 13 , November 2021 , pp. 1595 - 1601
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Abkallo, HM, Tangena, JA, Tang, J, Kobayashi, N, Inoue, M, Zoungrana, A, Colegrave, N and Culleton, R (2015) Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii. PLoS Pathogens 11, e1004628.10.1371/journal.ppat.1004628CrossRefGoogle Scholar
Alonso-Padilla, J, Abril, M, Alarcón de Noya, B, Almeida, IC, Angheben, A, Araujo Jorge, T, Chatelain, E, Esteva, M, Gascón, J, Grijalva, MJ, Guhl, F, Hasslocher-Moreno, AM, López, MC, Luquetti, A, Noya, O, Pinazo, MJ, Ramsey, JM, Ribeiro, I, Ruiz, AM, Schijman, AG, Sosa-Estani, S, Thomas, MC, Torrico, F, Zrein, M and Picado, A (2020) Target product profile for a test for the early assessment of treatment efficacy in Chagas disease patients: an expert consensus. PLoS Neglected Tropical Diseases 14, e0008035.CrossRefGoogle ScholarPubMed
Barros, JHS, Xavier, SCC, Bilac, D, Lima, VS, Dario, MA and Jansen, AM (2017) Identification of novel mammalian hosts and Brazilian biome geographic distribution of Trypanosoma cruzi TcIII and TcIV. Acta Tropica 172, 173–179.CrossRefGoogle ScholarPubMed
Bizai, ML, Peralta, R, Simonetto, A, Olivera, LV, Arias, EE, Dalla Costa, J, Manattini, S, Sione, W, Fabbro, D and Diez, C (2020) Geographic distribution of Trypanosoma cruzi genotypes detected in chronic infected people from Argentina. Association with climatic variables and clinical manifestations of Chagas disease. Infection, Genetics and Evolution 78, 104128.CrossRefGoogle ScholarPubMed
Blanchet, D, Brenière, SF, Schijman, AG, Bisio, M, Simon, S, Véron, V, Mayence, C, Demar-Pierre, M, Djossou, F and Aznar, C (2014) First report of a family outbreak of Chagas disease in French Guiana and posttreatment follow-up. Infection, Genetics and Evolution 28, 245–250.CrossRefGoogle ScholarPubMed
Burgos, JM, Altcheh, J, Bisio, M, Duffy, T, Valadares, HM, Seidenstein, ME, Piccinali, R, Freitas, JM, Levin, MJ, Macchi, L, Macedo, AM, Freilij, H and Schijman, AG (2007) Direct molecular profiling of minicircle signatures and lineages of Trypanosoma cruzi bloodstream populations causing congenital Chagas disease. International Journal for Parasitology 37, 1319–1327.CrossRefGoogle ScholarPubMed
Burgos, JM, Diez, M, Vigliano, C, Bisio, M, Risso, M, Duffy, T, Cura, C, Brusses, B, Favaloro, L, Leguizamon, MS, Lucero, RH, Laguens, R, Levin, MJ, Favaloro, R and Schijman, AG (2010) Molecular identification of Trypanosoma cruzi discrete typing units in end-stage chronic Chagas heart disease and reactivation after heart transplantation. Clinical Infectious Diseases 51, 85–95.CrossRefGoogle ScholarPubMed
Cafferata, ML, Toscani, MA, Althabe, F, Belizán, JM, Bergel, E, Berrueta, M, Capparelli, EV, Ciganda, Á, Danesi, E, Dumonteil, E, Gibbons, L, Gulayin, PE, Herrera, C, Momper, JD, Rossi, S, Shaffer, JG, Schijman, AG, Sosa-Estani, S, Stella, CB, Klein, K and Buekens, P (2020) Short-course benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): a non-inferiority randomized controlled trial study protocol. Reproductive Health 17, 128.CrossRefGoogle ScholarPubMed
Castro, JA, De Mecca, MM and Bartel, LC (2006) Toxic side effects of drugs used to treat Chagas’ disease (American trypanosomiasis). Human & Experimental Toxicology 25, 471–479.CrossRefGoogle Scholar
Cencig, S, Coltel, N, Truyens, C and Carlier, Y (2012) Evaluation of benznidazole treatment combined with nifurtimox, posaconazole or ambisome® in mice infected with Trypanosoma cruzi strains. International Journal of Antimicrobial Agents 40, 527–532.10.1016/j.ijantimicag.2012.08.002CrossRefGoogle ScholarPubMed
Chou, TC and Talalay, P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Advances in Enzyme Regulation 22, 27e55.CrossRefGoogle ScholarPubMed
Cummings, KL and Tarleton, RL (2003) Rapid quantitation of Trypanosoma cruzi in host tissue by real-time PCR. Molecular and Biochemical Parasitology 129, 53–59.CrossRefGoogle ScholarPubMed
Cunha, ELA, Torchelsen, FKVDS, Cunha, LM, Oliveira, MT, Reis, LES, Fonseca, KDS, Vieira, PMA, Carneiro, CM and Lana, M (2019) Benznidazole, itraconazole and their combination in the treatment of acute experimental Chagas disease in dogs. MethodsX 6, 2544–2552.CrossRefGoogle ScholarPubMed
Cura, CI, Duffy, T, Lucero, RH, Bisio, M, Péneau, J, Jimenez-Coello, M, Calabuig, E, Gimenez, MJ, Valencia Ayala, E, Kjos, SA, Santalla, J, Mahaney, SM, Cayo, NM, Nagel, C, Barcán, L, Málaga Machaca, ES, Acosta Viana, KY, Brutus, L, Ocampo, SB, Aznar, C, Cuba Cuba, CA, Gürtler, RE, Ramsey, JM, Ribeiro, I, VandeBerg, JL, Yadon, ZE, Osuna, A and Schijman, AG (2015) Multiplex real-time PCR assay using TaqMan probes for the identification of Trypanosoma cruzi DTUs in biological and clinical samples. PLoS Neglected Tropical Diseases 9, e0003765.CrossRefGoogle ScholarPubMed
Díaz, ML, Leal, S, Mantilla, JC, Molina-Berríosa, A, López-Muñoz, R, Solari, A, Escobar, P and González Rugeles, CI (2015) Acute Chagas outbreaks: molecular and biological features of Trypanosoma cruzi isolates, and clinical aspects of acute cases in Santander, Colombia. Parasites & Vectors 8, 608.CrossRefGoogle ScholarPubMed
Echeverría, LE, González, CI, Hernandez, JCM, Díaz, ML, Nieto, EJ, López-Romero, LA, Rivera, JD, Suárez, EU, Ochoa, SAG, Rojas, LZ and Morillo, CA (2020) Efficacy of the benznidazole+posaconazole combination therapy in parasitemia reduction: an experimental murine model of acute Chagas. Revista da Sociedade Brasileira de Medicina Tropical 53, e20190477.CrossRefGoogle ScholarPubMed
Fabrino, DL, Ribeiro, GA, Teixeira, L and Melo, RCN (2010) Histological approaches to study tissue parasitism during the experimental Trypanosoma cruzi infection. In Chiarini-Garcia, H and Melo, RCN (eds), Light Microscopy. New Jersey, USA: Humana Press, pp. 69–80.Google Scholar
Freitas, JM, Andrade, LO, Pires, SF, Lima, R, Chiari, E, Santos, RR, Soares, M, Machado, CR, Franco, GR, Pena, SD and Macedo, AM (2009) The MHC gene region of murine hosts influences the differential tissue tropism of infecting Trypanosoma cruzi strains. PLoS One 4, e5113.CrossRefGoogle ScholarPubMed
García, MC, Ponce, NE, Sanmarco, LM, Manzo, RH, Jimenez-Kairuz, AF and Aoki, MP (2016) Clomipramine and benznidazole act synergistically and ameliorate the outcome of experimental Chagas disease. Antimicrobial Agents and Chemotherapy 60, 3700–3708.CrossRefGoogle ScholarPubMed
Guedes, PM, Silva, GK, Gutierrez, FR and Silva, JS (2011) Current status of Chagas disease chemotherapy. Expert Review of Anti-infective Therapy 9, 609–620.10.1586/eri.11.31CrossRefGoogle ScholarPubMed
Guhl, F (2013) Epidemiología molecular de Trypanosoma cruzi. Revista Española de Salud Publica 87, 1–8.Google Scholar
Juiz, NA, Solana, ME, Acevedo, GR, Benatar, AF, Ramirez, JC, da Costa, PA, Macedo, AM, Longhi, SA and Schijman, AG (2017) Different genotypes of Trypanosoma cruzi produce distinctive placental environment genetic response in chronic experimental infection. PLoS Neglected Tropical Diseases 11, e0005436.CrossRefGoogle ScholarPubMed
Klaassen, CD and Aleksunes, LM (2010) Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Pharmacological Reviews 62, 1–96.10.1124/pr.109.002014CrossRefGoogle ScholarPubMed
Lachaud, L, Chabbert, E, Dubessay, P, Reynes, J, Lamothe, J and Bastien, P (2001) Comparison of various sample preparation methods for PCR diagnosis of visceral leishmaniasis using peripheral blood. Journal of Clinical Microbiology 39, 613–617.CrossRefGoogle ScholarPubMed
Lo Presti, MS, Esteves, BH, Moya, D, Bazán, PC, Strauss, M, Báez, AL, Pizzi, R, Quispe Ricalde, MA, Valladares, B, Rivarola, HW and Paglini-Oliva, PA (2014) Circulating Trypanosoma cruzi populations differ from those found in the tissues of the same host during acute experimental infection. Acta Tropica 133, 98–109.CrossRefGoogle ScholarPubMed
Macedo, AM, Oliveira, RP and Pena, SD (2002) Chagas disease: role of parasite genetic variation in pathogenesis. Expert Reviews in Molecular Medicine 4, 1–16.CrossRefGoogle ScholarPubMed
Medeiros, M, Araújo-Jorge, TC, Batista, WS, Da Silva, TMOA and De Souza, AP (2010) Trypanosoma cruzi infection: do distinct populations cause intestinal motility alteration?. Parasitology Research 107, 239–242.CrossRefGoogle Scholar
Messenger, LA, Miles, MA and Bern, C (2015) Between a bug and a hard place: Trypanosoma cruzi genetic diversity and the clinical outcomes of Chagas disease. Expert Review of Anti-Infective Therapy 13, 995–1029.CrossRefGoogle Scholar
Molina-Morant, D, Fernández, ML, Bosch-Nicolau, P, Sulleiro, E, Bangher, M, Salvador, F, Sanchez-Montalva, A, Ribeiro, ALP, de Paula, AMB, Eloi, S, Correa-Oliveira, R, Villar, JC, Sosa-Estani, S and Molina, I (2020) Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): study protocol for a multicentre randomized Phase II non-inferiority clinical trial. Trials 21, 328.CrossRefGoogle Scholar
Moraes, CB, Giardini, MA, Kim, H, Franco, CH, Araujo-Junior, AL, Schenkman, S, Chatelain, E and Freitas-Junior, LH (2014) Nitroheterocyclic compounds are more efficacious than CYP51 inhibitors against Trypanosoma cruzi: implications for Chagas disease drug discovery and development. Scientific Reports 4, 4703.CrossRefGoogle ScholarPubMed
Moreno, M, D'Avila, DA, Silva, MN, Galvão, LMC, Macedo, AM, Chiari, E, Dias Gontijo, E and Zingales, B (2010) Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease. Memórias do Instituto Oswaldo Cruz 105, 918–924.CrossRefGoogle Scholar
Moscatelli, G, Moroni, S, García Bournissen, F, González, N, Ballering, G, Schijman, A, Corral, R, Bisio, M, Freilij, H and Altcheh, J (2019) Longitudinal follow up of serological response in children treated for Chagas disease. PLoS Neglected Tropical Diseases 13, e0007668.CrossRefGoogle ScholarPubMed
Novaes, RD, Santos, EC, Cupertino, MC, Bastos, DS, Oliveira, JM, Carvalho, TV, Neves, MM, Oliveira, LL and Talvani, A (2015) Trypanosoma cruzi infection and benznidazole therapy independently stimulate oxidative status and structural pathological remodeling of the liver tissue in mice. Parasitology Research 114, 2873–2881.CrossRefGoogle ScholarPubMed
Pena, DA, Eger, I, Nogueira, L, Heck, N, Menin, A, Báfica, A and Steindel, M (2011) Selection of TcII Trypanosoma cruzi population following macrophage infection. Journal of Infectious Diseases 204, 478–486.CrossRefGoogle ScholarPubMed
Perdomo, VG, Rigalli, JP, Villanueva, SSM, Ruiz, ML, Luquita, MG, Echenique, CG and Catania, VA (2013) Modulation of biotransformation systems and ABC transporters by benznidazole in rats. Antimicrobial Agents and Chemotherapy 57, 4894–4902.CrossRefGoogle ScholarPubMed
Perez-Molina, JA and Molina, I (2018) Chagas disease. Lancet (London, England) 391, 82–94.10.1016/S0140-6736(17)31612-4CrossRefGoogle ScholarPubMed
Ragone, PG, Pérez Brandán, C, Monje Rumi, M, Tomasini, N, Lauthier, JJ, Cimino, RO, Uncos, A, Ramos, F, Alberti, A, D'Amato, AM, Basombrío, MA and Diosque, P (2015) Experimental evidence of biological interactions among different isolates of Trypanosoma cruzi from the Chaco region. PLoS One 10, e0119866.CrossRefGoogle ScholarPubMed
Rendon, D (2014) Alterations of mitochondria in liver but not in heart homogenates after treatment of rats with benznidazole. Human & Experimental Toxicology 33, 1066–1070.CrossRefGoogle Scholar
Resende, BC, Oliveira, ACS, Guañabens, ACP, Repolês, BM, Santana, V, Hiraiwa, PM, Pena, SDJ, Franco, GR, Macedo, AM, Tahara, EB, Fragoso, SP, Andrade, LO and Machado, CR (2020) The influence of recombinational processes to induce dormancy in Trypanosoma cruzi. Frontiers in Cellular and Infection Microbiology 10, 5.CrossRefGoogle ScholarPubMed
Revollo, S, Oury, B, Vela, A, Tibayrenc, M and Sereno, D (2019) In vitro benznidazole and nifurtimox susceptibility profile of Trypanosoma cruzi strains belonging to discrete typing units TcI, TcII, and TcV. Pathogens (Basel, Switzerland) 8, 197.Google ScholarPubMed
Ribeiro, V, Dias, N, Paiva, T, Hagström-Bex, L, Nitz, N, Pratesi, R and Hecht, M (2020) Current trends in the pharmacological management of Chagas disease. International Journal for Parasitology. Drugs and Drug Resistance 12, 7–17.CrossRefGoogle ScholarPubMed
Rodrigues Dos Santos, I, Melo, MF, de Castro, L, Hasslocher-Moreno, AM, do Brasil, PEAA, Silvestre de Sousa, A, Britto, C and Moreira, OC (2018) Exploring the parasite load and molecular diversity of Trypanosoma cruzi in patients with chronic Chagas disease from different regions of Brazil. PLoS Neglected Tropical Diseases 12, e0006939.CrossRefGoogle ScholarPubMed
Ruiz-Lancheros, E, Chatelain, E and Ndao, M (2019) Chagas disease treatment efficacy biomarkers: myths and realities. In: Altcheh, J, Freilij, H (eds), Chagas Disease. Birkhäuser Advances in Infectious Diseases. Cham: Springer, pp. 323–349. doi: 10.1007/978-3-030-00054-7_16.Google Scholar
Sales-Campos, H, Kappel, HB, Andrade, CP, Lima, TP, Mattos, ME Jr, de Castilho, A, Correia, D, Giraldo, LE and Lages-Silva, E (2014) A DTU-dependent blood parasitism and a DTU-independent tissue parasitism during mixed infection of Trypanosoma cruzi in immunosuppressed mice. Parasitology Research 113, 375–385.CrossRefGoogle Scholar
Sánchez-Valdéz, FJ, Padilla, A, Wang, W, Orr, D and Tarleton, RL (2018) Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure. eLife 7, e34039.CrossRefGoogle ScholarPubMed
Solana, ME, Celentano, AM, Tekiel, V, Jones, M and González Cappa, SM (2002) Trypanosoma cruzi: effect of parasite subpopulation on murine pregnancy outcome. Journal of Parasitology 88, 102–106.CrossRefGoogle ScholarPubMed
Strauss, M, Rodrigues, JHS, Lo Presti, MS, Bazán, PC, Báez, AL, Paglini-Oliva, P, Nakamura, CV, Bustamante, JM and Rivarola, HW (2018a) In vitro and in vivo drug combination for the treatment of Trypanosoma cruzi infection: a multivariate approach. Experimental Parasitology 189, 19–27.CrossRefGoogle Scholar
Strauss, M, Velázquez López, DA, Moya, DM, Bazán, PC, Báez, AL, Rivarola, HW, Paglini-Oliva, PA and Lo Presti, MS (2018b) Differential tissue distribution of Trypanosoma cruzi during acute experimental infection: further evidence using natural isolates. Molecular and Biochemical Parasitology 222, 29–33.CrossRefGoogle Scholar
Sulleiro, E, Silgado, A, Serre-Delcor, N, Salvador, F, Tavares de Oliveira, M, Moure, Z, Sao-Aviles, A, Oliveira, I, Treviño, B, Goterris, L, Sánchez-Montalvá, A, Pou, D, Molina, I and Pumarola, T (2020) Usefulness of real-time PCR during follow-up of patients treated with benznidazole for chronic Chagas disease: experience in two referral centers in Barcelona. PLoS Neglected Tropical Diseases 14, e0008067.CrossRefGoogle ScholarPubMed
Thomson, L, Denicola, A and Radi, R (2003) The trypanothione-thiol system in Trypanosoma cruzi as a key antioxidant mechanism against peroxynitrite- mediated cytotoxicity. Archives of Biochemistry and Biophysics 412, 55e64.CrossRefGoogle ScholarPubMed
Tolosa de Talamoni, N, Moya, M, Martini, C, López, B, Gallará, R and Ponzio, F (2010) Reglamentación para el cuidado y uso de animales de experimentación en dependencia de la Facultad de Ciencias Médicas y Facultad de Odontología. Comité Institucional para el Cuidado y Uso de Animales de Laboratorio. UNC.Google Scholar
Vela, A, Coral-Almeida, M, Sereno, D, Costales, JA, Barnabe´, C and Brenière, SF (2021) In vitro susceptibility of Trypanosoma cruzi discrete typing units (DTUs) to benznidazole: a systematic review and meta-analysis. PLoS Neglected Tropical Diseases 15, e0009269.CrossRefGoogle ScholarPubMed
Virreira, M, Torrico, F, Truyens, C, Alonso-Vega, C, Solano, M, Carlier, Y and Svoboda, M (2003) Comparison of polymerase chain reaction methods for reliable and easy detection of congenital Trypanosoma cruzi infection. The American Journal of Tropical Medicine and Hygiene 68, 574–582.10.4269/ajtmh.2003.68.574CrossRefGoogle ScholarPubMed
Wong, ML and Medrano, JF (2005) Real-time PCR for mRNA quantitation. BioTechniques 39, 75–85.CrossRefGoogle ScholarPubMed
Zhang, QG and Buckling, A (2016) Migration highways and migration barriers created by host-parasite interactions. Ecology Letters 19, 1479–1485.CrossRefGoogle ScholarPubMed
Zhang, L and Tarleton, RL (1999) Parasite persistence correlates with disease severity and localization in chronic Chagas’ disease. The Journal of Infectious Diseases 180, 480–486.CrossRefGoogle ScholarPubMed
Zhang, C and Yan, G (2019) Synergistic drug combinations prediction by integrating pharmacological data. Synthetic and Systems Biotechnology 4, 67–72.CrossRefGoogle ScholarPubMed
Zingales, B, Miles, MA, Campbell, DA, Tibayrenc, M, Macedo, AM, Teixeira, MM, Schijman, AG, Llewellyn, MS, Lages-Silva, E, Machado, CR, Andrade, SG and Sturm, NR (2012) The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infection, Genetics and Evolution 12, 240–253.CrossRefGoogle ScholarPubMed
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