Canine leishmaniasis: epidemiological risk and the experimental model

Objective—To conduct serologic surveillance for Leishmania spp in English Foxhounds from a kennel, as well as recipients of blood from these dogs, and determine whether L infantum organisms could be transmitted via blood transfusion. Design—Serologic prevalence survey. Animals—120 English Foxhounds and 51 dogs of various breeds receiving blood from these donors. Procedure—Foxhound blood donors, foxhound nondonors, and nonfoxhound blood recipient dogs were evaluated serologically for Leishmania spp by indirect fluorescent antibody testing. Dogs that received packed RBC (PRBC) transfusions from foxhound donors from mid-1996 through mid-2000 were identified. Furthermore, dogs were serologically evaluated if they had received fresh frozen plasma (FFP) transfusions in 1999 and 2000 from seropositive foxhound blood donors. Results—Thirty percent of the English Foxhounds were seropositive for Leishmania spp (titer ≥ 1:16), although the degree of seropositivity varied considerably during the period. Furthermore, ...

Transmission of visceral leishmaniasis through blood transfusions from infected English foxhounds to anemic dogs.

A phase III trial of efficacy of the FML-vaccine against canine kala-azar in an endemic area of Brazil (São Gonçalo do Amaranto, RN).

In public health terms, leishmaniases are diseases of humans and dogs, whereas, in epidemiological terms, Leishmania spp. are considered to represent infections of a wide variety of animals, which represent the natural reservoirs of the various parasite species involved. Humans and dogs (which may be considered secondary or 'accidental' hosts in the leishmanial life-cycle) often exhibit severe clinical signs and symptoms when infected, whereas reservoir hosts generally show a few, minor or no signs. This situation makes the definition of a suitable laboratory model a difficult one, since the various experimental hosts may behave either like a reservoir or an accidental host. This review discusses the concept of animal models for leishmaniases and provides a critical evaluation of the most common experimental models and their respective advantages and disadvantages. In this state-of-the-art review, particular emphasis is given to the value of using mouse, hamster, cotton-rat, dog and primate models, especially in the context of testing potential anti-leishmanial vaccines.

Experimental models for leishmaniasis and for testing anti-leishmanial vaccines.

Canine leishmaniosis caused by Leishmania infantum (Syn. L. chagasi) is an important zoonosis with a complex pathogenesis. Parasite transmission occurs via female sandflies that inject promastigotes into the skin of the host. The interaction between the parasite and skin immune system is influenced by the repeated infectious bites and the simultaneous intradermal injection of sandfly saliva. Amastigotes are transported via infected macrophages to the regional lymph nodes and finally dissemination may occur. The outcome of the infection depends on host factors (genetic background, cell-mediated and humoral immune response, cytokine milieu, concurrent diseases) and parasite virulence. Resistance may be breed-associated; it is characterized by low to undetectable antibody production and effective cell-mediated immunity, and is orchestrated by cytokines such as interleukin-2, interferon-gamma and tumour necrosis factor-alpha. Susceptibility may be genetically determined or acquired (advanced age, concurrent diseases); in these dogs, parasite multiplication goes unrestricted and overproduction of specific and nonspecific antibodies occurs, leading to multiple organ pathology. Resistance or susceptibility is not an all-or-nothing phenomenon and many intermediate phenotypes may be found. From a diagnostic point of view, although clinical cases are readily identified using microscopy and serology, investigation should not stop at this point and an extensive search for underlying diseases is advised, especially in aged dogs. Conversely, microscopy and conventional serology are frequently negative in asymptomatic infected dogs; to identify such dogs, polymerase chain reaction, evaluation of cutaneous delayed-type hypersensitivity, in vitro lymphocyte proliferation test to Leishmania antigen, and Western blotting may be employed.

Advances in the pathogenesis of canine leishmaniosis: epidemiologic and diagnostic implications.

Visceral leishmaniasis was experimentally induced in hamsters by the intracardiac inoculation of 10(7) amastigotes of Leishmania leishmania infantum of canine origin. At postinoculation (PI) days 7, 21, 42, and 63, hamsters were euthanatized. Body weights and total parasite numbers of the liver and spleen were determined. Gross and histologic evaluations of tissues were done. Dogs also were inoculated IV with 10(8) amastigotes/kg of body weight. Samples were obtained from dogs prior to infection and at biweekly PI intervals for CBC and serum chemical analysis, for lymphocyte blastogenic assay by use of blood leukocytes, and for ELISA to determine antileishmanial antibody titers. At PI week 12, dogs were necropsied; organ weights, tissue imprints of the liver and spleen, and histologic interpretations of tissues were obtained. Hamsters developed high parasite numbers within 7 days after inoculation, at which time the total parasite numbers in the liver (3.51 x 10(7) amastigotes) was observed to be approximately 11 times that in the spleen (2.93 x 10(6)). The liver had the highest parasite numbers throughout the infection period. Some infected hamsters became either cachectic and emaciated or ascitic. Two of the 10 infected hamsters died at PI days 54 and 58. Moderate to severe hepatosplenomegaly with granulomatous inflammatory reactions characterized by the presence of varied numbers of parasitized macrophages, giant cells, and hepatic Schaumann bodies were observed in infected hamsters. Infected dogs developed significantly altered hematologic values consisting of mild anemia and moderate leukopenia at PI weeks 8 to 12. Hyperproteinemia characterized by hyperglobulinemia (4.5 g/dl) was noticed at PI week 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of virulence and pathogenesis of a canine strain of Leishmania leishmania infantum in hamsters and dogs.

The leishmaniases are global health problems that affect both humans and animals. The availability of nonhuman primate models is desirable for such important areas as testing candidate vaccines and newly developed chemo- and immunotherapeutic agents. Visceral leishmaniasis was experimentally induced in African green monkeys (Cercopithecus aethiops) by intravenously inoculating 10(7) amastigotes/kg of body weight of either Leishmania leishmania donovani of human origin (group 1) or L. l. infantum of canine origin (group 2). The infected monkeys were monitored for 12 weeks. The monkeys developed persistent infections, became emaciated, and lost between 9 and 22% of their body weights. Splenomegaly developed by 6 to 10 weeks postinfection. All infected monkeys developed normocytic, normochromic anemia (3.5 to 3.8 x 10(6)/microliters), leukopenia (3,000 to 3,700/microliters), and neutropenia of varying severity. Hyperproteinemia with hyperglobulinemia (5.22 to 6.12 g/dl) was present in all monkeys to various degrees. Antibody responses gradually increased to peak values at 2 weeks postinfection in the L. l. donovani group and by 6 weeks postinfection in the L. l. infantum group. Lymphocyte blastogenesis proliferation responses were mildly decreased in all infected monkeys at 10 to 12 weeks postinfection. Parasite numbers were consistently higher in the livers than in spleens, and parasites were present in smears or cultures of the liver, spleen, bone marrow, and lymph nodes. Contrasting data between the two groups included 20-fold-higher parasite numbers in the livers (3.23 to 9.48 x 10(9)) and 39-fold-higher parasite numbers in the spleens (6.7 x 10(8) to 2.69 x 10(9)) of group 1. Granulomatous inflammatory reactions of various severity and intensity were observed in the liver, spleen, lymph nodes, thymus, and bone marrow of all infected monkeys. Within the granulomatous inflammatory reactions, clusters of macrophages, often containing amastigotes, were present. The morphologic changes in the bone marrow suggested a myelophthisic disease and those in lymph nodes and spleen suggested a B-cell proliferation. The clinicopathologic changes, mild suppression of cell-mediated immunity, and high antibody response in all infected monkeys indicated that African green monkeys can be a useful laboratory model for studying the clinicopathologic and immunopathologic changes induced by both L. l. donovani and L. l. infantum.

Comparative susceptibility of African green monkeys (Cercopithecus aethiops) to experimental infection with Leishmania leishmania donovani and Leishmania leishmania infantum.

Binhazim Aa

Papers

Determination of virulence and pathogenesis of a canine strain of Leishmania leishmania infantum in hamsters and dogs.

Comparative susceptibility of African green monkeys (Cercopithecus aethiops) to experimental infection with Leishmania leishmania donovani and Leishmania leishmania infantum.

Multiple spontaneous lesions in an aged spider monkey.