Initial and Long-Term Efficacy of a Lipid Emulsion of Amphotericin B Desoxycholate in the Management of Canine Leishmaniasis
Pentavalent antimonials, alone or in combination with allopurinol, are the most frequently drugs used in the management of canine leishmaniasis (CL). Despite clinical remission occurs in a majority of cases, most dogs remain parasitologically infected and relapses are frequent. It should be considered that if a clinical but not parasitological cure is achieved, dogs may act as a reservoir of the disease. Moreover, side effects and development of resistances must be considered. Amphotericin B desoxycholate (AmB) is a powerful leishmanicidal agent. Its use in dogs with CL it not very extended, due in part to its nephrotoxicity. Recently the initial effectiveness and toxicity of a new protocol using a lipid emulsion of AmB was assessed.2 The aim of this prospective study is to evaluate both, the initial and the long-term efficacy of this protocol in the treatment of dogs naturally infected with CL.
14 dogs showing clinical signs of CL and diagnosed after visualization of leishmania amastigotes in bone marrow samples were included in the study. The mean age was 4.4 years (range, 1.5-11 years). The mean weight was 26 kg (range, 5-37 kg). Six were males, all intact, and eight were females, 3 spayed. Breeds included Boxer (3), Belgian sheepdog (2), Giant Schnauzer (1), Rottweiler (1), American Pit-bull Terrier (1) and Mongrel (6). Laboratorial work-up at presentation and at the end of the treatment comprised a CBC, serum protein electrophoresis (SPE), biochemical profile, bone marrow aspirates, urinalysis and a urine protein/creatinine ratio (UP/C). Systolic blood pressure was determined using an ultrasonic Doppler flow detector. Due to nephrotoxic effects of AmB, pre-existing renal dysfunction observed in 4 dogs was treated before starting the protocol.
Treatment was administered twice a week by a peripheral vein infusion according to a published protocol.2 AmB initial dose was from 1 to 1.5 mg/kg and it was increased (up to 2 mg/kg) or reduced (to 0.8 mg/kg) according to the observed side effects and serum creatinine (SCr) value, which was determined just before each treatment. When SCr exceeded 2.5 mg/dl the treatment was stopped and the patient evaluated ten days later. Total administered dose of AmB to each dog ranged from 9.1 to 16.3 mg/kg; (mean 12.9 mg/kg) divided into 8 to 10 sessions (mean 8.57). Follow up included a complete clinical exam, SPE and PCR assay within the first three months after the treatment was completed and then at least twice a year.
Observed side effects included anorexia and/or vomiting within the first 36 hours of treatment, (24/121 treatments) and elevations in SCr greater than 2.5 mg/dl (3 /121 treatments). At the end of the treatment all dogs (14/14) were clinically cured, and no laboratorial abnormalities were observed, except in case 4 where a non-azotemic glomerulopathy was observed (UP/C: 2.7). Bone marrow examination did not show leishmania amastigotes in any of the 14 dogs. At the first follow-up examination all dogs were healthy with no abnormalities in SPE, and 13/14 were PCR negative. The dog which was PCR positive remained asymptomatic but PCR positive in a second examination performed three months later. He experienced a clinical and laboratorial relapse 5 months after the end of the treatment and was euthanasied at the owner's request. Three dogs became PCR positive at the 2nd follow-up performed within the first year after treatment; 2 of these dogs developed clinical signs and displayed alterations in their SPE, but the other one was asymptomatic. Of the 5 dogs followed longer than a year, 4 remained clinically cured and PCR negative at 18 (2 dogs), 22 (1 dog) and 24 (1 dog) months. The other one became PCR positive at the 3rd post-treatment examination performed 15 months after the end of the therapy. This dog was asymptomatic and no alterations were observed in the SPE.
AmB in lipid emulsion can be used safely in dogs with CL even in some cases with pre-existing renal dysfunctions. Initial effectiveness of this protocol must be considered excellent; all dogs were clinically cured when the treatment was finished and 13/14 were PCR negative 1 to 3 month after the end of the treatment. According to the results of the follow-up, a single negative PCR result in a recently treated dog can't not be interpreted like a complete cure. The author considers that a minimum of 3 consecutive negative PCR obtained during a period of 18 months would be necessary before a complete cure could be established.
1. Font A. Canine leishmaniasis. Proceedings of the 17th ACVIM Forum 17:630-632. Chicago,1999
2. Lamothe J. Activity of amphotericin B in lipid emulsion in the initial treatment of canine leishmaniasis. J Small Anim Pract. 2001 Apr;42(4):170-5.