Comparative study of the use of miltefosine, miltefosine plus allopurinol, and allopurinol in dogs with visceral leishmaniasis

Dias, Álvaro Felipe de Lima Ruy; Sorte, Eveline da Cruz Boa; Martins, Domingos Tabajara de Oliveira; Maruyama, Fernanda Harumi; Oliveira, Ruberlei Godinho de; Carvalho, Matheus Roberto de; Almeida, Arleana do Bom Parto Ferreira de; Teixeira, Anna Louisa de Souza; Mendonça, Adriane Jorge; Sousa, Valéria Régia Franco

doi:10.1016/j.exppara.2020.107947

Cited by 14 publications

(23 citation statements)

References 44 publications

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“…A correlation between the Leishmania antibody titer reduction, the clinical score trend and the decrease of the parasitic load has been reported (42)(43)(44)(45). Accordingly, in our study the percentage of dogs that reached the cut-off or negative value at D180 was minimal (two dogs out of 34), confirming that positive IFAT values may persist in clinically recovered dogs (46,47).…”

Section: Discussionsupporting

confidence: 82%

Comparison of Two Dosing Regimens of Miltefosine, Both in Combination With Allopurinol, on Clinical and Parasitological Findings of Dogs With Leishmaniosis: A Pilot Study

et al. 2020

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Miltefosine (MIL)–allopurinol combination therapy administered at standard dosage is effective to treat canine leishmaniosis, nevertheless for some dogs the digestive tolerance of MIL is not acceptable. This study evaluates an alternative therapeutic protocol by using a modified dosage of MIL to increase its effectiveness and improve the digestive tolerance. Thirty-four Leishmania infantum owned naturally infected dogs were included and monitored for 180 days. The dogs were allocated in two randomized groups: Group X−18 dogs treated with MIL registered dose of 2 mg/kg, oral administration, once daily, for 28 days; Group Y−16 dogs treated with 1.2 mg/kg for 5 days followed by 2.5 mg/kg for 25 days. Both groups were also treated with allopurinol. Digestive tolerance was monitored by adverse events observation. Treatments effectiveness was evaluated by monitoring the reduction of clinical score, the improvement of clinicopathological abnormalities, the reduction of parasitological load by PCR and the number of relapses. 16.6% dogs of group X and 12.5% dogs of group Y showed treatment associated adverse events. The reduction of clinical score was 61.7% for group X and 71.6% for group Y. All dogs showed an improvement of laboratory parameters after treatment. Quantitative PCR showed better results in group Y compared to group X; relapses were only registered in four dogs of group X. The modified protocol demonstrates a better trend of results in term of tolerance, clinical effectiveness, parasitological load reduction and relapses control, suggesting it could be considered for new large-scale studies.

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Section: Discussionsupporting

confidence: 82%

Comparison of Two Dosing Regimens of Miltefosine, Both in Combination With Allopurinol, on Clinical and Parasitological Findings of Dogs With Leishmaniosis: A Pilot Study

et al. 2020

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“…Miltefosine interferes in parasite metabolic pathways and the induction of apoptosis ( Soto & Soto, 2006 ). It is considered the second-choice drug used for leishmaniosis in dogs ( Dias et al., 2020 ; Solano-Gallego et al., 2011 ). The main side effects in dogs are usually vomiting and diarrhea ( Solano-Gallego et al., 2011 ).…”

Section: Resultsmentioning

confidence: 99%

Leishmaniosis caused by Leishmania infantum in ferrets: Update review

Villanueva‐Saz

Giner

Marteles

et al. 2022

Veterinary and Animal Science

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Leishmaniosis in domestic ferrets ( Mustela putorius furo ) is a disease caused by Leishmania infantum , a parasite transmitted through the bite of an infected female phlebotomine sand fly. Among vertebrates, the dog is the primary domestic reservoir of the parasite; however, other domestic animals can be implicated such as cats. The first description of a clinical case of leishmaniosis in domestic ferrets was reported recently. As a result, new knowledge has been published including empirically based treatment protocols, confirmatory techniques to detect the presence of the parasite infection and seasonal variation in the antibodies against Leishmania in apparently healthy domestic ferrets. The most common clinical signs observed are enlargement of peripheral lymph nodes and skin lesions such as papular and/or ulcerative dermatitis. Additionally, the most frequent laboratory alterations seen are hyperproteinaemia with hyperglobulinaemia and biochemical analytes alterations depending on the affected tissue. Two different therapeutic protocols have been described to treat domestic ferrets with leishmaniosis: meglumine antimoniate plus allopurinol protocol or miltefosine plus allopurinol protocol. These treatment protocols seemed to be able to control the Leishmania infection, although the presence of xanthinuria could be detected. The susceptibility of domestic ferrets to Leishmania infantum , the clinical picture, treatment of infected animals and prevention are poorly understood, due to the scarcity of recent description in the literature. Different proposed diagnostic algorithms have been included for domestic ferrets with suspected leishmaniosis, clinically healthy domestic ferrets and animals as blood donors. In this sense, the present review provides updated data on scientific knowledge of leishmaniosis in ferrets.

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“…Additionally, allopurinol (used in combination with miltefosine in the dog treated herein) is a leishmaniostatic drug [31,32]. There is a previous report of cross-resistance between meglumine antimoniate and allopurinol, but not between these drugs and miltefosine or amphotericin B [28].…”

Section: Graphical Abstractmentioning

confidence: 99%

Increased Leishmania infantum resistance to miltefosine and amphotericin B after treatment of a dog with miltefosine and allopurinol

Gonçalves

Campos

Gonçalves³

et al. 2021

Parasites Vectors

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Background Leishmania infantum is the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine was authorized to treat canine leishmaniasis (CanL) in Brazil in 2017, but there is a persistent fear of the emergence of parasites resistant not only to this drug but, through cross-resistance mechanisms, also to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are drivers of parasite virulence. In this context, the aim of this study was to analyze the impact of treating a dog with miltefosine and allopurinol on the generation of parasites resistant to miltefosine, amphotericin B and meglumine antimoniate. Methods In vitro susceptibility tests were conducted against miltefosine, amphotericin B and meglumine antimoniate with T0 (parasites isolated from a dog before treatment with miltefosine plus allopurinol), T1 (after 1 course of treatment) and T2 (after 2 courses of treatment) isolates. The rates of cell proliferation, infectivity and metacyclogenesis of the isolates were also evaluated. Results The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. An increasing trend in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. Conclusion The data indicates an increased L. infantum resistance to miltefosine and amphotericin B after the treatment of a dog with miltefosine plus allopurinol. Further studies with a larger number of L. infantum strains isolated from dogs with varied immune response profiles and undergoing different treatment regimes, are advocated. Graphical Abstract

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Comparative study of the use of miltefosine, miltefosine plus allopurinol, and allopurinol in dogs with visceral leishmaniasis

Cited by 14 publications

References 44 publications

Comparison of Two Dosing Regimens of Miltefosine, Both in Combination With Allopurinol, on Clinical and Parasitological Findings of Dogs With Leishmaniosis: A Pilot Study

Comparison of Two Dosing Regimens of Miltefosine, Both in Combination With Allopurinol, on Clinical and Parasitological Findings of Dogs With Leishmaniosis: A Pilot Study

Leishmaniosis caused by Leishmania infantum in ferrets: Update review

Increased Leishmania infantum resistance to miltefosine and amphotericin B after treatment of a dog with miltefosine and allopurinol

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