Research Article
Unresponsiveness of Experimental Canine Leishmaniosis
to a New Amphotericin B Formulation
Leticia Hernández,
1
Francisco Bolás-Fernández,
2
Ana Montoya,
1
Rocío Checa,
1
Diana Dado,
1
Rosa Gálvez,
1
Dolores R. Serrano,
3
Juan J. Torrado,
3
Domenico Otranto,
4
Maria S. Latrofa,
4
and Guadalupe Miró
1
1
Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Avenida Puerta de Hierro s/n,
28040 Madrid, Spain
2
Departamento de Parasitolog´ ıa, Facultad de Farmacia, Universidad Complutense, Plaza Ramon y Cajal, 28040 Madrid, Spain
3
Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramon y Cajal,
28040 Madrid, Spain
4
Department of Veterinary Medicine, University of Bari, Valenzano, 70010 Bari, Italy
Correspondence should be addressed to Guadalupe Mir´ o; gmiro@ucm.es
Received 10 September 2014; Accepted 7 December 2014
Academic Editor: Maria J. Morilla
Copyright © 2015 Leticia Hern´ andez et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Tis study was designed to evaluate the efcacy and safety of a novel free polyaggregated amphotericin B (FPA) formulation
used to treat experimental canine leishmaniosis (CanL) caused by Leishmania infantum. Eight healthy beagles were intravenously
challenged with 5 × 10
7
promastigotes per mL of L. infantum. One year afer infection, they received an intravenous dose of FPA
(5 mg/kg) every 2 weeks three times. Dogs were assessed monthly for clinical signs, serology, and parasite detection during a follow-
up period of 6 months. Transient adverse efects (i.e., hypotension, diarrhea, bodyweight loss, fever, and asthenia) were observed
within 24–48 hours afer treatment in 4 animals. In three dogs mean clinical signs scores were reduced. Antibody titers measured
by immunofuorescence antibody test (IFAT) had signifcantly diminished at the end of the study, although according to bone
marrow smears and cultures a high percentage of dogs tested positive for the parasite at 6 months posttreatment (PT6). Real-time
quantitative PCR (rtQ-PCR) on blood, bone marrow, and urine samples revealed the presence of parasitic DNA in all animals at
PT6, although blood loads of the parasite were reduced. Tese fndings indicate that FPA at the dosing regimen used did not achieve
clinical or parasitological cure in dogs experimentally infected with L. infantum.
1. Introduction
Canine leishmaniosis (CanL) is a serious zoonotic disease
caused by protozoa of the genus Leishmania (Kinetoplas-
tida, Trypanosomatidae). Te disease is endemic in many
countries worldwide, including the Mediterranean basin,
Portugal, South Africa, and Latin America [1], and is of
major veterinary and public health concern since domestic
dogs are the main reservoir of Leishmania infantum [2].
Infected female sand fies of the genus Phlebotomus (Diptera,
Psychodidae) are the biological vectors for L. infantum in
Europe. Tese hematophagous insects transmit the disease by
inoculating metacyclic promastigotes in the skin of vertebrate
hosts [3].
In dogs, the incubation period of the disease may last
from 3 months to several years [4]. Importantly, in areas
where the disease is endemic, a large number of infected
dogs do not develop clinical signs or clinicopathological
abnormalities and are referred to as clinically healthy infected
dogs [1]; however, they remain infective to sand fies. CanL is
a systemic disease that displays a wide spectrum of clinical
signs, such as generalized lymphadenomegaly, weight loss,
lethargy, skin lesions, and other less common signs like
polyuria/polydypsia, digestive disorders, ocular lesions, and
Hindawi Publishing Corporation
Advances in Pharmaceutics
Volume 2015, Article ID 160208, 13 pages
http://dx.doi.org/10.1155/2015/160208