19 month old, male, American Foxhound, Canis familiaris, dog.This male American Foxhound dog along with a sibling was donated to Iowa State University because both were seropositive for Leishmania spp. This animal was born in August of 2005 to a Leishmania positive bitch, and both siblings became serologically positive for Leishmania in January of 2007. Following seroconversion the dog became anemic, thrombocytopenic and leukopenic. Upon presentation, the dog exhibited epistaxis and was progressively losing weight.
The animal was thin to emaciated with minimal adipose tissue in body cavities and subcutaneous tissues.Â The liver was diffusely and markedly enlarged (1.65kg), pale, and firm with a diffuse finely granular texture.Â The spleen was diffusely and markedly enlarged (38g) and pale with finely granular capsular surface texture.Â All lymph nodes, including peripheral, mesenteric and mediastinal nodes were markedly enlarged.Â Bilaterally the kidneys were moderately enlarged and diffusely pale, and there was little peri-renal adipose tissue.
Kidney: Multifocal glomeruli have thickened Bowmans capsules and approximately 60-70% of glomeruli have markedly thickened and prominent capillary loops with numerous synechiae.Â Multiple glomeruli are shrunken and hypocellular (sclerosis).Â Within the interstitium, there are multifocal to coalescing accumulations of inflammatory cells, primarily lymphocytes, plasma cells and macrophages, with moderate numbers of macrophages containing one or more 1-2 um round to oval basophilic organisms.Â Cytologically these organisms are ovoid, 1-3 um in diameter, with a round, basophilic nucleus and a rod-shaped kinetoplast.
Adrenal glands: Multifocally throughout the adrenal cortex, there are multiple foci of lymphocytes, plasma cell, and macrophages.Â Many of the macrophages contain numerous small intracellular organisms as described above.Â
- 1.Â Kidney:
- a.Â Glomerulonephritis, membranous, severe, chronic, diffuse, with multifocal glomerulosclerosis.Â
- b.Â Interstitial nephritis, lymphoplasmacytic and granulomatous, severe, chronic, multifocal to coalescing, with intra-histiocytic organisms consistent with Leishmania species.
- 2.Â Adrenal gland: Adrenalitis, granulomatous and lymphoplasmacytic, moderate, chronic, multifocal with intra-histiocytic organisms consistent with Leishmania species.
A complete blood count revealed a non-regenerative anemia and thrombocytopenia, while a chemistry panel showed elevation in alkaline phosphatase and alanine transferase as well as hypoproteinemia.Â On urinalysis there was 4+ protein in the urine.Â Spleen and bone marrow samples were culture positive for Leishmania by the Centers for Disease Control and Prevention (CDC).Â Real-time PCR on whole blood performed at ISU and the CDC were positive for Leishmania infantum.
The changes in the kidney and adrenal gland are consistent with disseminated visceral leishmaniasis.Â Parasites were also present within macrophages in the liver, spleen, lymph nodes, pancreas and bone marrow (not submitted for evaluation).Â Leishmania infantum is a protozoal parasite that causes visceral leishmaniasis.Â Natural hosts include rodents, small mammals, dogs, and humans, although infection is usually accidental .Â Leishmaniasis is transmitted to the host by the sandfly bite after which the promastigote form of the parasite is phagocytosed by macrophages .Â Once within the host cell the parasite transforms into amastigotes and multiples, eventually leading to systemic spread of the parasite.Â Parasite control requires the induction of a TH1 immune response characterized by production of interferon gamma and interleukin 12 that function to activate infected macrophages to kill the intracellular pathogen .Â Visceral leishmaniasis is characterized by fever, weight loss, hepatomegaly, splenomegaly, skin lesions and epistaxis .Â Histologically there are focal granulomas with intra-histiocytic organisms in affected organs as well as lymphofollicular hyperplasia within the spleen and lymph nodes .Â Membranous glomerulonephritis is a common finding in both canine and human patients with visceral leishmaniasis and is secondary to antigen-antibody complex formation and subsequent deposition within the mesangium of the glomerulus .Â
Although endemic in southern Central and South America, the Middle East, Central Asia and Africa, this disease is also present in the United States and sporadic cases have been reported, usually travelers returning from an endemic area .Â In the year 2000, a foxhound kennel in New York reported four foxhounds to be infected with L.Â infantum .Â The sandfly vector is present within the United States, although at this time it has not be determined if sandfly transmission of Leishmania occurs in this country.Â Other mechanisms have been postulated in transmission of canine visceral leishmaniasis and include vector-independent modes such as breeding and direct contact.Â There may also be a genetic or breed susceptibility to infection, as numerous foxhounds have tested positive and infection appears to be widespread within this breed in the United States, indicating a possible public health threat .Â
1.Â Kidney: Glomerulonephritis, membranoproliferative, global, diffuse, subacute, marked with multifocal to coalescing lymphoplasmacytic interstitial nephritis, protein casts, and intrahistiocytic amastigotes, etiology consistent with Leishmania sp., American Foxhound (Canis familiaris), canine.
2.Â Adrenal gland: Adrenalitis, histiocytic, neutrophilic, and plasmacytic, multifocal, moderate, with intrahistiocytic amastigotes, etiology consistent with Leishmania sp.
Leishmania are protozoan parasites of the family Trypanosomidae, order Kinetoplastida. They survive within the cytoplasm of mammalian macrophages as amastigotes (leishmanial form) that are 2.0_m in diameter with a vesicular nucleus, no flagella and a small basophilic kinetoplast.
There are three forms of Leishmaniasis:
1.Â Cutaneous (oriental sore) L.Â tropica Mediteranean sea
2.Â Mucocutaneous (espundia) L.Â braziliensis Central America
3.Â Visceral (kala-azar) L.Â donovani Europe, Africa and Asia
The primary insect vectors for Leishmania sp.Â include the phlebotomine sand flies (Lutzomyia sp.Â and Phlebotomus sp.).Â Of the fourteen Lutzomyia sp.Â in North America, three are known to be capable of transmitting Leishmania mexicana (cutaneous leishmaniasis in Mexico and Texas). Other forms of transmission that have been implicated include mechanical transfer through ticks, shared needles, sexual contact, and bite wounds, as well as transmammary and transplacental transmission.
Upon phagocytosis by macrophages, the organism survives within the phagolysosome despite the activated proteinases and the low environmental pH (4.5-5.0). Studies of the cutaneous form of leishmaniasis in mice caused by L.Â major indicate immunity depends on an IL-12 driven CD4+, TH1-type response with production of IFN gamma.Â A CD4+, TH2-type response with production of IL-4 and IL-10 results in susceptibility.
The initial case of visceral Leishmaniasis in a fox hound in North America occurred in 1980. Since that time, visceral leishmaniasis caused by the Leishmania donovani complex (L.Â donovani, L.Â infantum, L.Â chagasi) has been identified in 21 states in the U.S.Â and 2 Canadian provinces.
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