Benznidazole, itraconazole, and their combination for the treatment of chronic experimental Chagas disease in dogs

Cunha, Eleonora Lima Alves; Torchelsen, Fernanda Karoline Vieira da Silva; Fonseca, Kátia da Silva; Sousa, Lucas Resende Dutra; Vieira, Paula Melo Abreu; Carneiro, Cláudia Martins; Pinto, Kelerson Mauro de Castro; Torres, Rosália Morais; Lana, Marta de

doi:10.1016/j.exppara.2022.108266

Cited by 6 publications

(5 citation statements)

References 48 publications

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“…As a perspective, it would be interesting to evaluate the parameters in a more advanced chronic stage of ChD, in which it would be possible to analyze the drug’s effect in the long term. On the other hand, nitazoxanide could be used in combination with benznidazole to improve its trypanocidal effectiveness, as noted by several authors when combining different drugs with benznidazole [ 22 , 23 , 31 , 43 , 44 , 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Nitazoxanide: A Drug Repositioning Compound with Potential Use in Chagas Disease in a Murine Model

et al. 2023

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Chagas disease (ChD), caused by Trypanosoma cruzi, is the most serious parasitosis in the western hemisphere. Benznidazole and nifurtimox, the only two trypanocidal drugs, are expensive, difficult to obtain, and have severe side effects. Nitazoxanide has shown to be effective against protozoa, bacteria, and viruses. This study aimed to evaluate the nitazoxanide efficacy against the Mexican T. cruzi Ninoa strain in mice. Infected animals were orally treated for 30 days with nitazoxanide (100 mg/kg) or benznidazole (10 mg/kg). The clinical, immunological, and histopathological conditions of the mice were evaluated. Nitazoxanide- or benznidazole-treated mice had longer survival and less parasitemia than those without treatment. Antibody production in the nitazoxanide-treated mice was of the IgG1-type and not of the IgG2-type as in the benznidazole-treated mice. Nitazoxanide-treated mice had significantly high IFN-γ levels compared to the other infected groups. Serious histological damage could be prevented with nitazoxanide treatment compared to without treatment. In conclusion, nitazoxanide decreased parasitemia levels, indirectly induced the production of IgG antibodies, and partially prevented histopathological damage; however, it did not show therapeutic superiority compared to benznidazole in any of the evaluated aspects. Therefore, the repositioning of nitazoxanide as an alternative treatment against ChD could be considered, since it did not trigger adverse effects that worsened the pathological condition of the infected mice.

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Section: Discussionmentioning

confidence: 99%

Nitazoxanide: A Drug Repositioning Compound with Potential Use in Chagas Disease in a Murine Model

et al. 2023

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“…Modified treatment protocols, such as that described here, and combination treatment are options being further explored. 17,25,26 In conclusion, prophylactic and early benznidazole treatment…”

Section: Discussionmentioning

confidence: 92%

“…The complexity of T cruzi infection related to parasite load, strain, and duration of time infected combined with variable host immune response leads to unpredictable outcomes and persistent challenges in identifying successful antiparasitic treatments. Modified treatment protocols, such as that described here, and combination treatment are options being further explored 17,25,26 …”

Section: Discussionmentioning

confidence: 99%

Positive clinical outcome using a modified dosing regimen of benznidazole in dogs at high risk for infection or acutely infected with Trypanosoma cruzi

Lim,

Collins,

Hamer

et al. 2024

Veterinary Internal Medicne

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Trypanosoma cruzi infection in dogs can cause heart failure and sudden death with few treatment options available. A litter of 4 dogs living in a T cruzi endemic area were randomized to prophylaxis and nonprophylaxis groups as part of a study evaluating a modified benznidazole dosing regimen administered twice weekly to prevent T cruzi infection during a vector transmission season. The 2 dogs that received prophylaxis remained healthy without T cruzi infection or cardiac disease for >2 years. One dog that did not receive prophylaxis died unexpectedly with acute T cruzi–induced pancarditis, and the second dog tested positive for T cruzi and developed complex arrhythmias with markedly increased cardiac troponin I and improved with a higher benznidazole treatment dose. Although the small sample size precludes definitive conclusions, we describe the potential clinical benefit of prophylactic and early treatment with modified benznidazole dosing regimens for dogs with T cruzi infection.

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“…In an effort to improve the effectiveness of BNZ, it has been tested in combination with other drugs [ 33 , 34 ] or it has been administered in different presentations, such as micro- and nanoparticles [ 35 , 36 ]; in addition, other molecules have been used as alternative treatments [ 37 , 38 , 39 ]. The prevailing need to find a targeted treatment for CD that is effective in the acute and chronic stages, mainly against the cardiac presentation, and that does not have serious side effects, led to the study of NTZ and EOW as treatment in the canine model.…”

Section: Discussionmentioning

confidence: 99%

“…Cunha et al [ 34 ] evaluated dogs infected with a BNZ-resistant T. cruzi strain and treated with BNZ or itraconazole (ITZ) or with both drugs for 60 days. Polymerase chain reaction (PCR) was negative in 2 of 3 animals in the BNZ + ITZ group, 2 of 5 in the BNZ group, and 4 of 5 in the ITZ group; the blood culture performed at month 24 was negative in all groups and the serum samples evaluated by ELISA remained reactive in all treated animals [ 34 ]. In contrast, in the present study, the detection of IgG antibodies indicated a specific anti- T. cruzi immune response from 3 mpi to 9.5 mpi.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Nitazoxanide and Electrolyzed Oxiding Water in Treating Chagas Disease in a Canine Model

Rodríguez-Morales,

Mendoza-Téllez,

Morales-Salinas

et al. 2023

Pharmaceutics

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Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, and affects seven million people in Latin America. Side effects and the limited efficacy of current treatment have led to new drug research. The objective of this work was to evaluate the effectiveness of nitazoxanide (NTZ) and electrolyzed oxidizing water (EOW) in a canine model of experimental CD. Náhuatl dogs were infected with the T. cruzi H8 strain and NTZ- or EOW-treated orally for 10 days. Seronegativity was shown at 12 months post-infection (mpi) in the NTZ-, EOW-, and benznidazole (BNZ)-treated groups. The NTZ and BNZ groups had high levels of IFN-γ, TNF-α, IL-6, IL-12B, and IL-1β at 1.5 mpi and low levels of IL-10. Electrocardiographic studies showed alterations from 3 mpi and worsening at 12 mpi; NTZ treatment produced fewer cardiac pathomorphological changes compared to EOW, similar to BNZ treatment. There was no cardiomegaly in any group. In conclusion, although NTZ and EOW did not prevent changes in cardiac conductivity, they were able to avoid the severity of heart damage in the chronic phase of CD. NTZ induced a favorable proinflammatory immune response after infection, being a better option than EOW as a possible treatment for CD after BNZ.

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Benznidazole, itraconazole, and their combination for the treatment of chronic experimental Chagas disease in dogs

Cited by 6 publications

References 48 publications

Nitazoxanide: A Drug Repositioning Compound with Potential Use in Chagas Disease in a Murine Model

Nitazoxanide: A Drug Repositioning Compound with Potential Use in Chagas Disease in a Murine Model

Positive clinical outcome using a modified dosing regimen of benznidazole in dogs at high risk for infection or acutely infected with Trypanosoma cruzi

Effectiveness of Nitazoxanide and Electrolyzed Oxiding Water in Treating Chagas Disease in a Canine Model

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