MEDICINE UPDATE: DIAGNOSTICS AND TREATMENTS Review of Equine Cutaneous Leishmaniasis: Not Just a Foreign Animal Disease Sarah M. Reuss, VMD, Diplomate ACVIM Although long considered to be a foreign animal disease, cutaneous leishmaniasis has recently been identified in two horses in Florida with no history of international travel. Both horses were diag- nosed with Leishmania siamensis, an organism with zoonotic potential. Practitioners in the United States should have this disease on their differential list for horses with ulcers and nodules on the ears, head, and neck. Author’s address: University of Florida, Department of Large Animal Clinical Sciences, PO Box 100136, Gainesville, FL 32610; e-mail: sreuss@ufl.edu. © 2013 AAEP. 1. Introduction the parasites reside as intracellular amastigotes Leishmaniasis is a zoonotic disease most well de- within macrophages, where they replicate by binary scribed in people and dogs; however, cutaneous fission. When infected macrophages rupture, sur- leishmaniasis has been documented in horses rounding macrophages phagocytize the amastigotes around the world. Although cases have been seen and become infected. The disease is endemic in in the United States, most of these horses had a tropical and subtropical regions but is spreading history of recent importation from endemic areas. with global climate change. There are more than In 2012, the first autochthonous (non–travel-re- 30 species of Leishmania with a complex classifica- lated) case of equine cutaneous leishmaniasis in the tion scheme. The species of Leishmania vary with United States was published with the discovery of region, and different species are often incriminated Leishmania siamensis in a Morgan mare in Florida.1 to cause different disease manifestations. In the Since that time, a second horse in Florida (also with Eastern Hemisphere, the “Old World” species Leish- no history of international travel) has been diag- mania donovani, Leishmania infantum, Leishmania nosed with L siamensis.a Therefore, leishmaniasis tropica, and Leishmania aethiopica are commonly should be included in the differential list for horses found. In the Western Hemisphere, the “New in the United States with cutaneous lesions regard- World” species Leishmania braziliensis and Leish- less of their travel history or country of origin. mania mexicana are frequently found, most com- The goal of this article is to raise the awareness of monly in South and Central America. However, this disease amongst equine practitioners by review- L mexicana has been reported as the causative ing the etiology, pathogenesis, clinical syndromes, organism of some vector-transmitted outbreaks of diagnosis, and treatment of leishmaniasis. cutaneous leishmaniasis in people and dogs in Texas.2 L siamensis is a recently described species 2. Etiology/Method of Transmission that had not been previously reported in North Leishmaniasis is caused by the obligate intracellu- America until it was determined to be the etiologic lar protozoa of the genus Leishmania. In mammals, organism in both Florida horse cases.1 L siamensis NOTES 256 2013 ր Vol. 59 ր AAEP PROCEEDINGS MEDICINE UPDATE: DIAGNOSTICS AND TREATMENTS was first described as the cause of autochthonous visceral leishmaniasis in two men in Southern Thailand3,4 but has also been identified as the cause of equine cutaneous lesions in central Eu- rope5 and a cow in Switzerland.6 In all mammalian species affected with leishman- iasis, the primary mode of transmission is believed to be by various species of sand flies. The promas- tigote stages of the protozoa are transmitted in the saliva of the female sand fly at the moment of blood feeding.7 Each species of Leishmania is adapted to transmission in certain species of sandflies: Phlebo- tomus spp in the Old World and Lutzomyia spp in the New World. The vector in equine transmission in the United States remains unidentified; however, the phlebotomine sand flies Lutzomyia shannoni and Lutzomyia vexator are found in Florida, where the two autochthonous equine cases were diag- nosed.8 Lutzomyia shannoni is known to use both humans and other mammals as hosts, and it has been incriminated as a vector of L braziliensis in Central and South America. It has also been shown experimentally to be capable of becoming infected with L infantum when feeding on ill L in- fantum-infected dogs.9 However, it is not known whether L shannoni will permit Leishmania de- velopment into infectious metacyclic parasites. Leishmania mexicana is considered endemic in south-central Texas, where the organism is main- tained within the ecosystem by small rodents and is presumably spread by a Lutzomyia spp (possibly Fig. 1. Cutaneous leishmaniasis in the left pinna of a 10-year- Lutzomyia diabolica).2 Although vector-borne old Morgan horse mare in Florida. transmission is the primary means of spread be- tween dogs in endemic areas, it is thought that vertical transmission (transplacental and trans- mammary) is probably the major means of spread in In Europe, L infantum has been reported as the dogs in non-endemic areas of the United States.10 causative agent of cutaneous leishmaniasis in The frequency of vertical transmission in endemic horses in Germany,14 Spain,15 and Portugal.16 regions is difficult to determine because of the high Recently, a report from central Europe identified an likelihood of vector contact. Ticks have been shown organism with 98% identity to L siamensis as the experimentally to be capable of transmission in cause of cutaneous lesions in four horses.4 Whereas dogs, and horizontal transmission by direct contact equine leishmaniasis is documented in Puerto Rico,17 with blood has also been shown.10 it is rarely seen in the continental United States. Historically, cutaneous leishmaniasis in the United 3. Clinical Manifestations States was seen in horses with a history of interna- tional travel or recent importation. Although autoch- Equine thonous cases may have been observed2, the first Cutaneous leishmaniasis has been documented in documented case occurred in 2011.1 To date, only horses around the world. Lesions are most com- cutaneous lesions have been documented in horses. monly observed as nodules on the head, pinnae, scrotum, legs, and neck. They may be solitary or Human multiple, and are often ulcerated (Fig. 1). No other Leishmaniasis is the second leading parasitic cause signs are seen, and visceral lesions have not been of death in people, after malaria. There are ap- reported. Equine leishmaniasis was first reported proximately 1.8 million new cases per year, making in Argentina in 1927. In South America, L brazil- this a top priority for the World Health Organiza- iensis has been identified as the causative organism tion. Three basic syndromes are seen in people: in horses.11,12 In one endemic region of Brazil, 26 cutaneous, mucocutaneous, and visceral. Cutane- horses, donkeys, and mules were examined. Cuta- ous disease presents as painless nodules, plaques, or neous lesions were found in 10 animals, and eight ulcers. In general, lesions heal spontaneously in animals (30.8% of the examined population) had immunocompetent individuals. Mucocutaneous le- parasites seen on histopathology of ulcer margins.13 sions involve the nares, nasal septum, pharynx, lar- AAEP PROCEEDINGS ր Vol. 59 ր 2013 257 MEDICINE UPDATE: DIAGNOSTICS AND TREATMENTS ynx, and genitalia; and they can occur concurrently or 1 to 5 years after resolution of cutaneous lesions. These lesions will not heal spontaneously. Visceral leishmaniasis, otherwise known as “kala azar,” is a chronic, insidious disease that may be preceded by cutaneous lesions. Visceral leishmaniasis is usu- ally associated with species of the Leishmania don- ovani complex (L donovani, L infantum, Leishmania chagasi) and L tropica. Clinical signs include fe- ver, weight loss, anemia, anorexia, cough, diarrhea, and darkening of the skin. Splenomegaly, hepato- megaly, lymphadenopathy, thrombocytopenia, and leukopenia may all be present as the parasite in- vades the reticuloendothelial system. Visceral dis- ease is fatal unless treated, and treated patients will remain carriers and can recrudesce if immuno- suppressed. Canine Fig. 2. Fine-needle aspirate of an ulcerated mass from a horse Dogs are the most commonly affected domestic spe- with cutaneous leishmaniasis exhibiting an intracellular amasti- cies, with 63% to 80% seropositivity in endemic ar- gote (arrow). Photo courtesy of Dr. Mark Dunbar. eas in which they are thought to be the primary reservoir for L infantum and maintain the disease in domestic cycles.10 In endemic areas, all breeds of dogs are affected. Dogs, like humans, can develop amastigotes. Immunohistochemistry can be used cutaneous or visceral disease. Cutaneous lesions to confirm the diagnosis of leishmaniasis and has can present as nonpruritic exfoliative dermatitis, been performed successfully in the horse.5,14,17 nodules, ulcers, and long, brittle nails. Visceral Culture and qPCR can be performed by the Cen- disease results in lethargy, weight loss, anorexia, ters for Disease Control and Prevention or by vari- anemia, splenomegaly, epistaxis, hematuria, me- ous university research labs. Isoenzyme analysis lena, chronic renal failure, and death. Ocular le- of cultured parasites has been the conventional ap- sions have also been reported and include proach for species identification. However, PCR conjunctivitis, keratitis, and uveitis. The majority and sequence analysis can identify the organism to of cases of canine leishmaniasis in the United