• 1. World Health Organization. First WHO report on neglected tropical diseases: working to overcome the global impact of neglected tropical diseases. Available at: www.who.int/neglected_diseases/2010report/en/. Accessed Feb 11, 2018.

    • Search Google Scholar
    • Export Citation
  • 2. Morillo CA, Marin-Neto JA, Avezum A, et al. Randomized trial of benznidazole for chronic Chagas’ cardiomyopathy. N Engl J Med 2015;373:12951306.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Bern C. Chagas’ disease. N Engl J Med 2015;373:1882.

  • 4. Andrade SG. The influence of the strain of Trypanosoma cruzi in placental infections in mice. Trans R Soc Trop Med Hyg 1982;76:123128.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Shikanai-Yasuda MA, Carvalho NB. Oral transmission of Chagas disease. Clin Infect Dis 2012;54:845852.

  • 6. Bern C, Montgomery SP. An estimate of the burden of Chagas disease in the United States. Clin Infect Dis 2009;49:e52e54.

  • 7. Nieto PD, Boughton R, Dorn PL, et al. Comparison of two immunochromatographic assays and the indirect immunofluorescence antibody test for diagnosis of Trypanosoma cruzi infection in dogs in south central Louisiana. Vet Parasitol 2009;165:241247.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Tomlinson MJ, Chapman, WL Jr, Hanson WL, et al. Occurrence of antibody to Trypanosoma cruzi in dogs in the southeastern United States. Am J Vet Res 1981;42:14441446.

    • Search Google Scholar
    • Export Citation
  • 9. Kjos SA, Snowden KF, Craig TM, et al. Distribution and characterization of canine Chagas disease in Texas. Vet Parasitol 2008;152:249256.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Tenney TD, Curtis R, Snowden KF, et al. Shelter dogs as sentinels for Trypanosoma cruzi transmission across Texas. Emerg Infect Dis 2014;20:13231326.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Curtis-Robles R, Snowden KF, Dominguez B, et al. Epidemiology and molecular typing of Trypanosoma cruzi in naturally-infected hound dogs and associated triatomine vectors in Texas, USA. PLoS Negl Trop Dis 2017;11:e0005298.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. AVMA. US pet ownership & demographics sourcebook. Scha-umburg, Ill: AVMA, 2012.

  • 13. Barr SC. Canine Chagas’ disease (American trypanosomiasis) in North America. Vet Clin North Am Small Anim Pract 2009;39:10551064.

  • 14. Barr SC, Gossett KA, Klei TR. Clinical, clinicopathologic, and parasitologic observations of trypanosomiasis in dogs infected with North American Trypanosoma cruzi isolates. Am J Vet Res 1991;52:954960.

    • Search Google Scholar
    • Export Citation
  • 15. Berger SL, Palmer RH, Hodges CC, et al. Neurologic manifestations of trypanosomiasis in a dog. J Am Vet Med Assoc 1991;198:132134.

    • Search Google Scholar
    • Export Citation
  • 16. Vitt JP, Saunders AB, O'Brien MT, et al. Diagnostic features of acute Chagas myocarditis with sudden death in a family of Boxer dogs. J Vet Intern Med 2016;30:12101215.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Elizari MV, Chiale PA. Cardiac arrhythmias in Chagas’ heart disease. J Cardiovasc Electrophysiol 1993;4:596608.

  • 18. Barr SC, Simpson RM, Schmidt SP, et al. Chronic dilatative myocarditis caused by Trypanosoma cruzi in two dogs. J Am Vet Med Assoc 1989;195:12371241.

    • Search Google Scholar
    • Export Citation
  • 19. Barr SC, Holmes RA, Klei TR. Electrocardiographic and echocardiographic features of trypanosomiasis in dogs inoculated with North American Trypanosoma cruzi isolates. Am J Vet Res 1992;53:521527.

    • Search Google Scholar
    • Export Citation
  • 20. Snowden, Karen F, Kjos, Sonia A. American trypanosomiasis. In: Greene CE, ed. Infectious diseases of the dog and cat. 4th ed. St Louis: Elsevier-Saunders, 2012;722729.

    • Search Google Scholar
    • Export Citation
  • 21. Meurs KM, Anthony MA, Slater M, et al. Chronic Trypanosoma cruzi infection in dogs: 11 cases (1987–1996). J Am Vet Med Assoc 1998;213:497500.

    • Search Google Scholar
    • Export Citation
  • 22. Santos FM, Lima WG, Gravel AS, et al. Cardiomyopathy prognosis after benznidazole treatment in chronic canine Chagas’ disease. J Antimicrob Chemother 2012;67:19871995.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Drugs for Neglected Diseases initiative. Drug trial for leading parasitic killer of the Americas shows mixed results but provides new evidence for improved therapy. Available at: www.dndi.org/2013/media-centre/press-releases/e1224/. Accessed Feb 11, 2018.

    • Search Google Scholar
    • Export Citation
  • 24. Urbina JA. Specific treatment of Chagas’ disease: current status and new developments. Curr Opin Infect Dis 2001;14:733741.

  • 25. Urbina JA, Docampo R. Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol 2003;19:495501.

  • 26. Viotti R, Vigliano C, Armenti H, et al. Treatment of chronic Chagas’ disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J 1994;127:151162.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Pecoul B, Batista C, Stobbaerts E, et al. The BENEFIT trial: where do we go from here? PLoS Negl Trop Dis 2016;10:e0004343.

  • 28. Fairlamb AH, Patterson S. Current and future prospects of nitro-compounds as drugs for trypanosomiasis and leishmaniasis [published online ahead of print Apr 26, 2018]. Curr Med Chem doi: 10.2174/0929867325666180426164352.

    • Search Google Scholar
    • Export Citation
  • 29. 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;81:755759.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Toledo MJ, Bahia MT, Veloso VM, et al. Effects of specific treatment on parasitological and histopathological parameters in mice infected with different Trypanosoma cruzi clonal genotypes. J Antimicrob Chemother 2004;53:10451053.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Urbina JA. Recent clinical trials for the etiological treatment of chronic Chagas disease: advances, challenges and perspectives. J Eukaryot Microbiol 2015;62:149156.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Sales Junior PA, Molina I, Fonseca Murta SM, et al. Experimental and clinical treatment of Chagas disease: a review. Am J Trop Med Hyg 2017;97:12891303.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Buckner FS, Urbina JA. Recent developments in sterol 14-demethylase inhibitors for Chagas disease. Int J Parasitol Drugs Drug Resist 2012;2:236242.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Urbina JA. Parasitological cure of Chagas disease: is it possible? Is it relevant? Mem Inst Oswaldo Cruz 1999;94(suppl 1):349355.

  • 35. Molina I, Jordi P, Salvador F, et al. Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease. N Engl J Med 2014;370:18991908.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. Paniz-Mondolfi AE, Pérez-Alvarez A, Lanza G, et al. Amiodarone and itraconazole: a rational therapeutic approach for the treatment of chronic Chagas’ disease. Chemotherapy 2009;55:228233.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Apt W, Arribada A, Zulantay I, et al. Treatment of Chagas’ disease with itraconazole: electrocardiographic and parasitological conditions after 20 years of follow-up. J Antimicrob Chemother 2013;68:21642169.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38. Drugs for Neglected Diseases initiative. Drug trial for leading parasitic killer of the Americas shows mixed results but provides new evidence for improved therapy. Available at: www.dndi.org/media-centre/press-releases/1700-e1224.html?highlight=WyJlMTIyNCJd. Accessed Mar 9, 2019.

    • Search Google Scholar
    • Export Citation
  • 39. Benaim G, Sanders JM, Garcia-Marchán Y, et al. Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J Med Chem 2006;49:892899.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40. Benaim G, Paniz Mondolfi AE. The emerging role of amiodarone and dronedarone in Chagas disease. Nat Rev Cardiol 2012;9:605609.

  • 41. Veiga-Santos P, Barrias ES, Santos JF, et al. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi. Int J Antimicrob Agents 2012;40:6171.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42. Benaim B, Garcia CR. Targeting calcium homeostasis as the therapy of Chagas’ disease and leishmaniasis - a review. Trop Biomed 2011;28:471481.

    • Search Google Scholar
    • Export Citation
  • 43. Bellera CL, Balcazar DE, Alberca L, et al. Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects. J Chem Inf Model 2013;53:24022408.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44. Mawby DI, Whittemore JC, Genger S, et al. Bioequivalence of orally administered generic, compounded, and innovator-formulated itraconazole in healthy dogs. J Vet Intern Med 2014;28:7277.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45. Márquez ME, Concepción JL, González-Marcano E, et al. Detection of Trypanosoma cruzi by polymerase chain reaction. Methods Mol Biol 2016;1392:125141.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46. 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.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47. Urbina JA, Vivas J, Lazardi K, et al. Antiproliferative effects of delta 24(25) sterol methyl transferase inhibitors on Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies. Chemotherapy 1996;42:294307.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48. Adesse D, Azzam EM, Meirelles Mde N, et al. Amiodarone inhibits Trypanosoma cruzi infection and promotes cardiac cell recovery with gap junction and cytoskeleton reassembly in vitro. Antimicrob Agents Chemother 2011;55:203210.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49. TDR disease Reference Group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis, World Health Organization. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis: technical report of the TDR disease Reference Group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis. Geneva: World Health Organization, 2012.

    • Search Google Scholar
    • Export Citation
  • 50. Tanowitz HB, Scherer PE, Mota MM, et al. Adipose tissue: a safe haven for parasites? Trends Parasitol 2017;33:276284.

  • 51. Sanmarco LM, Eberhardt N, Ponce NE, et al. New insights into the immunobiology of mononuclear phagocytic cells and their relevance to the pathogenesis of cardiovascular diseases. Front Immunol 2018;8:1921.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52. Calvet CM, Melo TG, Garzoni LR, et al. Current understanding of the Trypanosoma cruzi-cardiomyocyte interaction. Front Immunol 2012;3:327.

    • Search Google Scholar
    • Export Citation
  • 53. Perfect JR, Savani DV, Durack DT. Uptake of itraconazole by alveolar macrophages. Antimicrob Agents Chemother 1993;37:903904.

  • 54. Felton T, Troke PF, Hope WW. Tissue penetration of antifungal agents. Clin Microbiol Rev 2014;27:6888.

  • 55. Morissette G, Ammoury A, Rusu D, et al. Intracellular sequestration of amiodarone: role of vacuolar ATPase and macroautophagic transition of the resulting vacuolar cytopathology. Br J Pharmacol 2009;157:15311540.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 56. Debbas NM, Du Cailar C, Sassine A, et al. Determination of cardiac and plasma drug levels during long-term amiodarone therapy. Eur J Clin Invest 1983;13:123127.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 57. McKee J, Rabinow B, Cook C, et al. Nanosuspension formulation of itraconazole eliminates the negative inotropic effect of Sporanox in dogs. J Med Toxicol 2010;6:331336.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 58. Combs TP, Nagajyothi JF, Mukherjee S, et al. The adipocyte as an important target cell for Trypanosoma cruzi infection. J Biol Chem 2005;280:2408524094.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 59. Prentice AG, Glasmacher A. Making sense of itraconazole pharmacokinetics. J Antimicrob Chemother 2005;56(suppl 1):i17i22.

  • 60. Brien JF, Jimmo S, Brennan FJ, et al. Disposition of amiodarone and its proximate metabolite, desethylamiodarone, in the dog for oral administration of single-dose and short-term drug regimens. Drug Metab Dispos 1990;18:846851.

    • Search Google Scholar
    • Export Citation
  • 61. Boothe DM. Small animal clinical pharmacology and therapeutics. St Louis: Elsevier-Saunders, 2012; 382.

  • 62. Perdomo VG, Rigalli JP, Luquita MG, et al. Up-regulation of ATP-binding cassette transporters in the THP-1 human macrophage cell line by the antichagasic benznidazole. Mem Inst Oswaldo Cruz 2016;111:707711.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 63. Richle RW, Raaflaub J. Difference of effective antitrypanosomal dosages of benznidazole in mice and man. Chemotherapeutic and pharmacokinetic results. Acta Trop 1980;37:257261.

    • Search Google Scholar
    • Export Citation
  • 64. Benznidazole [package insert]. Florham Park, NJ: Exeltis USA, 2017. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2017/2095701b1.pdf. Accessed Sep 20, 2018.

    • Search Google Scholar
    • Export Citation
  • 65. Perin L, Moreira da Silva R, Fonseca KD, et al. Pharmacokinetics and tissue distribution of benznidazole after oral administration in mice. Antimicrob Agents Chemother 2017;61:e02410e02416.

    • Search Google Scholar
    • Export Citation
  • 66. Bern C, Kjos S, Yabsley MJ, et al. Trypanosoma cruzi and Chagas’ disease in the United States. Clin Microbiol Rev 2011;24:655681.

  • 67. Hodo CL, Rodriguez JY, Curtis-Robles R, et al. Repeated cross-sectional study of Trypanosoma cruzi in shelter dogs in Texas, in the context of Dirofilaria immitis and tick-borne pathogen prevalence. J Vet Intern Med 2019;33:158166.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 68. Guedes PM, Veloso VM, Tafuri WL, et al. The dog as model for chemotherapy of the Chagas’ disease. Acta Trop 2002;84:917.

  • 69. Cançado JR. Long term evaluation of etiological treatment of Chagas disease with benznidazole. Rev Inst Med Trop São Paulo 2002;44:2937.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 70. Caldas IS, Menezes APJ, Diniz LF, et al. Parasitaemia and parasitic load are limited targets of the aetiological treatment to control the progression of cardiac fibrosis and chronic cardiomyopathy in Trypanosoma cruzi-infected dogs. Acta Trop 2019;189:3038.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 71. Cançado JR. Criteria of Chagas disease cure. Mem Inst Oswaldo Cruz 1999;94(suppl 1):331335.

  • 72. Murcia L, Carrilero B, Ferrer F, et al. Success of benznidazole chemotherapy in chronic Trypanosoma cruzi-infected patients with a sustained negative PCR result. Eur J Clin Microbiol Infect Dis 2016;35:18191827.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 73. Veloso VM, Carneiro CM, Toledo MJ, et al. Variation in susceptibility to benznidazole in isolates derived from Trypanosoma cruzi parental strains. Mem Inst Oswaldo Cruz 2001;96:10051011.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 74. Sarkar S, Strutz SE, Frank DM, et al. Chagas disease risk in Texas. PLoS Negl Trop Dis 2010;4:e836.

  • 75. Kjos SA, Snowden KF, Olson JK. Biogeography and Trypanosoma cruzi infection prevalence of Chagas disease vectors in Texas, USA. Vector Borne Zoonotic Dis 2009;9:4150.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 76. Beard CB, Young DG, Butler JF, et al. First isolation of Trypanosoma cruzi from a wild-caught Triatoma sanguisuga (LeConte) (Hemiptera: Triatominae) in Florida, U.S.A. J Parasitol 1988;74:343344.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 77. AVMA. One Health-Summary. Available at: www.avma.org/KB/Resources/Reports/Pages/One-Health146.aspx. Accessed Mar 16, 2019.

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Investigation of a combination of amiodarone and itraconazole for treatment of American trypanosomiasis (Chagas disease) in dogs

Roy Madigan1Animal Hospital of Smithson Valley, 286 Singing Oaks, Ste 113, Spring Branch, TX 78070.

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Sean Majoy2LTC Daniel E. Holland Military Working Dog Hospital, 1219 Knight St, Joint Base San Antonio-Lackland, Lackland AFB, TX 78236.

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Kristine Ritter2LTC Daniel E. Holland Military Working Dog Hospital, 1219 Knight St, Joint Base San Antonio-Lackland, Lackland AFB, TX 78236.

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Juan Luis Concepción3Laboratorio de Enzimología de Parásitos, Facultad de Ciencias, Universidad de Los Andes, Mérida 5101, Mérida, Venezuela.

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María Elizabeth Márquez3Laboratorio de Enzimología de Parásitos, Facultad de Ciencias, Universidad de Los Andes, Mérida 5101, Mérida, Venezuela.

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Sasha Caribay Silva3Laboratorio de Enzimología de Parásitos, Facultad de Ciencias, Universidad de Los Andes, Mérida 5101, Mérida, Venezuela.

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Alexandra Pérez Alvarez5Infectious Diseases Research Branch, Venezuelan Science Incubator and the Zoonosis and Emerging Pathogens Regional Collaborative Network, Av Intercomunal Barquisimeto-Acarigua, Urb Los Rastrojos, Cabudare 3023, Lara, Venezuela.

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Abstract

OBJECTIVE

To evaluate clinical, serologic, parasitological, and histologic outcomes of dogs with naturally occurring Trypanosoma cruzi infection treated for 12 months with amiodarone and itraconazole.

ANIMALS

121 dogs from southern Texas and southern Louisiana.

PROCEDURES

Treatment group dogs (n = 105) received a combination of amiodarone hydrochloride (approx 7.5 mg/kg [3.4 mg/lb], PO, q 24 h, with or without a loading dosage protocol) and itraconazole (approx 10 mg/kg [4.5 mg/lb], PO, q 24 h, adjusted to maintain a plasma concentration of 1 to 2 μg/mL) for 12 months. Control group dogs (n = 16) received no antitrypanosomal medications. Serologic assays for anti-T cruzi antibodies, PCR assays for T cruzi DNA in blood, and physical evaluations were performed 1, 6, 9, 12, and 24 months after study initiation. Adverse events were recorded. Outcomes of interest were recorded and compared between groups.

RESULTS

86 of 105 treatment group dogs and 8 of 16 control group dogs survived and completed the study (5/19 and 6/7 deaths of treatment and control group dogs, respectively, were attributed to T cruzi infection). Mean survival time until death attributed to T cruzi was longer (23.19 vs 15.64 months) for the treatment group. Results of PCR assays were negative for all (n = 92) tested treatment group dogs (except for 1 dog at 1 time point) from 6 to 24 months after study initiation. Clinical improvement in ≥ 1 clinical sign was observed in 53 of 54 and 0 of 10 treatment and control group dogs, respectively; adverse drug events were minor and reversible.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested efficacy of this trypanocidal drug combination for the treatment of T cruzi infection in dogs.

Abstract

OBJECTIVE

To evaluate clinical, serologic, parasitological, and histologic outcomes of dogs with naturally occurring Trypanosoma cruzi infection treated for 12 months with amiodarone and itraconazole.

ANIMALS

121 dogs from southern Texas and southern Louisiana.

PROCEDURES

Treatment group dogs (n = 105) received a combination of amiodarone hydrochloride (approx 7.5 mg/kg [3.4 mg/lb], PO, q 24 h, with or without a loading dosage protocol) and itraconazole (approx 10 mg/kg [4.5 mg/lb], PO, q 24 h, adjusted to maintain a plasma concentration of 1 to 2 μg/mL) for 12 months. Control group dogs (n = 16) received no antitrypanosomal medications. Serologic assays for anti-T cruzi antibodies, PCR assays for T cruzi DNA in blood, and physical evaluations were performed 1, 6, 9, 12, and 24 months after study initiation. Adverse events were recorded. Outcomes of interest were recorded and compared between groups.

RESULTS

86 of 105 treatment group dogs and 8 of 16 control group dogs survived and completed the study (5/19 and 6/7 deaths of treatment and control group dogs, respectively, were attributed to T cruzi infection). Mean survival time until death attributed to T cruzi was longer (23.19 vs 15.64 months) for the treatment group. Results of PCR assays were negative for all (n = 92) tested treatment group dogs (except for 1 dog at 1 time point) from 6 to 24 months after study initiation. Clinical improvement in ≥ 1 clinical sign was observed in 53 of 54 and 0 of 10 treatment and control group dogs, respectively; adverse drug events were minor and reversible.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested efficacy of this trypanocidal drug combination for the treatment of T cruzi infection in dogs.

Supplementary Materials

    • Supplementary Appendix S1 (PDF 71 kb)

Contributor Notes

Address correspondence to Dr. Madigan (roytmadigan@yahoo.com).