Evaluation of miltefosine for the treatment of dogs naturally infected with L. infantum (=L. chagasi) in Brazil

Abstract

Dogs naturally infected with Leishmania Infantum (=L. chagasi) were treated with miltefosine using different therapeutic regimens. The animals were evaluated for clinical evolution, biochemical parameters, parasite load (by real-time PCR), cytokine levels and humoral response. After treatment and during the following 24 months, there was progressive clinical improvement and complete recovery in 50% (7/14) of the treated animals. There was a decrease in the smear positivity of the bone marrow after treatment, and there was also a gradual and constant decrease in positive cultures at the end of the follow-up period. However, the PCR detection of parasite DNA remained positive. In general, all animals presented a significant increase in parasite load 6 months after treatment. The IFN-γ levels in all the groups tended to increase during follow-up period, regardless of the miltefosine dose administered. The IL-4 and IL-10 levels of the animals tended to decrease during follow-up, except after 300 days when only IL-10 increased. The serum antibodies identified antigens that ranged from 116 kDa to less than 29 kDa in the Western blot assay. Furthermore, 300 days after treatment, qualitative and quantitative differences in the antigen profiles were observed. Antigens of 97 and 46 kDa were the most intensely recognized. Higher levels of antigen-specific Leishmania IgG were detected before and 300 days after treatment in all groups. Taking together, the improvement in the clinical symptoms was not followed by parasitological clearance, suggesting that treatment with miltefosine is not recommended, especially in endemic areas like Brazil, where children are the major victims and dogs are involved in the maintenance of the parasite cycle.

Immunotherapy and Immunochemotherapy in Visceral Leishmaniasis: Promising Treatments for this Neglected Disease

“…Careful use of this drug should be mandatory, since resistance can be easily induced in in vitro experiments (85). Miltefosine has recently emerged as a potential tool for CVL treatment, and its use has been evaluated in monotherapy and in combination with other drugs (86, 87). There are no nephrotoxic effects reported, and vomiting is the most common side effect in dogs (88).…”

Use of a Recombinant Cysteine Proteinase from Leishmania (Leishmania) infantum chagasi for the Immunotherapy of Canine Visceral Leishmaniasis

“…Canine VL control is based on either treatment or euthanasia of infected animals. However, treatment of canine leishmaniasis with drugs successfully used for human VL shows low efficacy and induces the development of parasitic resistance to these drugs [7]–[10]. The WHO thus strongly recommends that the same drugs should not be used for treatment of dogs and humans in a same area [2].…”

Intra-abdominal Aspergillosis due to Aspergillus fumigatus in a Dog

“…Prednisolone administration for 6 weeks along with canine monocytic ehrlichiosis and leishmaniosis may have resulted in a suppression of cellular immunity (De Luna et al, 1999, Harrus et al, 2003, Saridomichelakis, 2009) that permitted uninhibited fungal invasion of abdominal organs. Negative PCR for Leishmania may be attributed to previous treatment with miltefosine that reduces tissue parasitic load (Manna et al, 2008, Mateo et al, 2009, Andrade et al, 2011 and to PCR examination of kidney tissue which is not optimal for the detection of the parasite (Costa et al, 2003, Plevraki et al, 2006.…”