First study on efficacy and tolerability of a new alkylphosphocholine molecule (oleylphosphocholine—OlPC) in the treatment of canine leishmaniosis due to Leishmania infantum

Abstract

The alkylphosphocholine oleylphosphocholine (OlPC) represents a potential new therapy for the treatment of canine leishmaniosis caused by Leishmania infantum. The aim of the present study was to evaluate the efficacy and safety of OlPC in a small cohort of dogs naturally infected with L. infantum and defined as clinically sick (LeishVet stages II and III). A total of eight dogs were included in the study and were treated orally with 4 mg/kg OlPC for 14 days. Dogs were assessed at the clinical and parasitological level at four time points during a total follow-up period of 90 days (before treatment and at 15, 30, and 90 days post-treatment onset). Ln-PCR, real-time quantitative PCR, antibody testing (IFAT), and culture of bone marrow aspirates were evaluated at the four time points. OlPC treatment induced a rapid and satisfactory clinical recovery in terms of clinical score reduction and weight gain, and treatment efficacy was found to be associated with a decrease in bone marrow parasitic load. Serological titers measured by IFAT were stable in any of the treated dogs at any time point after treatment. OlPC was well tolerated and no severe adverse events were noted in any of the treated dogs; even some dogs showed slight intestinal disorders. This proof-of-principle study is the first to show that short oral treatment with OlPC improves clinical signs of canine L. infantum leishmaniosis, highlighting the need to perform additional studies to optimize the dosing regimen and to assess long-term treatment efficacy of this drug.

Management of canine leishmaniosis in endemic SW European regions: a questionnaire-based multinational survey

“…A reliable diagnosis of CanL requires quantitative serological methods guided by an exhaustive evaluation of clinical signs and clinicopathological abnormalities [18,23]. Quantitative serology is appropriate for diagnosis in clinical practice and for treatment follow-up [18,23,29]. However, it has to be performed in specialized laboratories.…”

“…Real-time PCR is an advanced technique that can quantify Leishmania loads in infected dog tissues. However, although it is useful for diagnosis and the follow-up of treated dogs [29,70,71], its results are difficult to interpret due to their inconsistency such that very sick dogs may show low parasite loads and vice-versa. Under this same section, the reported use of routine diagnostic tests such as protein electrophoresis and immunohistochemistry should help improve the diagnosis of CanL [21,72].…”

“…Combinations of meglumine antimoniate or miltefosine with allopurinol (a leishmaniostatic agent) have been widely used and considered first line treatment against CanL since they are the most effective [19,26-28]. Other drugs have been also used such as amphotericin B, aminosidine, pentamidine, metronidazole and spiramycin combined, enrofloxacin, marbofloxacin, ketoconazole and oleylphosphocholine with variable efficacy [18,23,29]. More recently, the immunomodulator domperidone has been approved for veterinary use and could be useful to treat non-severe clinical cases [30].…”

Direct Comparison of the Efficacy and Safety of Oral Treatments with Oleylphosphocholine (OlPC) and Miltefosine in a Mouse Model of L. major Cutaneous Leishmaniasis

“…In addition, although no direct comparison with miltefosine was performed, the clinical efficacy of OlPC against L. infantum canine leishmaniasis (CanL) was also demonstrated in naturally infected dogs using a 14-day regimen of 4 mg/kg/day [16], a daily dose exceeding the maximum tolerated dose of miltefosine in that species (recommended miltefosine regimen in dogs: 2 mg/kg for 28 days). Therefore overall, OlPC is better tolerated than miltefosine and has better efficacy (i.e.…”

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

“…Furthermore, short oral treatment with OlPC improves clinical signs of canine L. infantum leishmaniasis. 166 The pharmacokinetic profiles of OlPC, administered either in water or as a liposomal preparation, have also been reported recently. 167 Natural agent, namely andrographolide, is a diterpenoid lactone extracted from the leaves of Andrographis paniculata, with strong antiparasitic and antileishmanial activity.…”