1 EEDA/IAT Web-Based Course • DZ Incursions • Visceral Leishmaniasis in Foxhounds • ©2012 CFSPH Visceral Leishmaniasis in Foxhounds in the United States, 2000-present Canine visceral leishmaniasis caused by Leishmania infantum is endemic in the Mediterranean Basin, Latin America and parts of Asia. Before 2000, a case would appear occasionally in the U.S., usually in a dog with a history of travel to an endemic area. In 2000, dogs in a foxhound kennel in the northeastern U.S. presented with an unusual clinical syndrome and were diagnosed with this protozoal infection. Since then, the disease has spread and has been found in foxhounds living in 22 states and two Canadian provinces; it is now considered endemic in foxhounds and foxhound-crosses in the U.S. is disease has human health implications; however, there have been no cases of human L. infantum infection acquired in North America to date. First Cases In February 2000, a small animal medicine resident, a clinical pathologist, and two fourth-year veterinary students from North Carolina State University (NCSU) diagnosed Leishmania infection in a foxhound, from a hunt club in Dutchess County, New York, that was wintering in the southern U.S. e dog had been taken to NCSU by the manager of the foxhound kennel, who reported that other dogs in the kennel were experiencing a similar, undiagnosed illness. e kennel had been operating as a working foxhound kennel for nearly 100 years. In August 1999, the foxhounds experienced an unusual illness. e clinical signs included wasting, anorexia, weakness, renal failure, skin lesions, exercise intolerance, and exhaustion. Several of the dogs had been euthanized and necropsied by the kennel’s private practitioner, who observed splenomegaly, hepatomegaly, and renal pathology. e kennel lost 18 dogs to this illness. During October and November 1999, the kennel was losing one dog per week. e dogs had been tested for a variety of tick-borne pathogens in October. e results indicated that they were antibody positive to various Ehrlichia, Babesia, and Rickettsia organisms. e dogs were treated with an insecticide to control the ticks. Various treatments, such as doxycycline and oxytetracycline, were attempted, but did not resolve the clinical illness. Imidocarb treatment (commonly used to treat Babesia infections in dogs) was initiated, but it appeared to be killing some of the hounds and so it was stopped. At NCSU, Leishmania organisms were identified by direct observation in bone marrow and joint tap samples obtained at necropsy of one dog. Because leishmania is a zoonotic pathogen, Edward Breitschwerdt, professor of Veterinary Internal Medicine at NCSU, reported the diagnosis of canine leishmaniasis to the Center for Disease Control and Prevention (CDC). e CDC began working with the Dutchess County (NY) Department of Health, the Walter Reed Army Institute of Research, the New York State Department of Agriculture, the New York State Department of Health, and the North Carolina State University College of Veterinary Medicine to investigate the outbreak. Serologic testing showed that 46 % of the hounds in the kennel had positive titers to Leishmania. Of the positive dogs, half had died and 13 dogs were ill. Canine Leishmaniasis in the U.S. Clinically ill foxhound Dog, bone marrow. e bone marrow contains hematopoietic precursors and macrophages with numerous intracytoplasmic Leishmania sp. organisms. e elongate organisms are distinguished by the central round dark basophilic kinetoplast structure
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1EEDA/IAT Web-Based Course • DZ Incursions • Visceral Leishmaniasis in Foxhounds • ©2012 CFSPH
Visceral Leishmaniasis in Foxhounds in the United States, 2000-presentCanine visceral leishmaniasis caused by Leishmania infantum is endemic in the Mediterranean Basin, Latin America and parts of Asia. Before 2000, a case would appear occasionally in the U.S., usually in a dog with a history of travel to an endemic area. In 2000, dogs in a foxhound kennel in the northeastern U.S. presented with an unusual clinical syndrome and were diagnosed with this protozoal infection. Since then, the disease has spread and has been found in foxhounds living in 22 states and two Canadian provinces; it is now considered endemic in foxhounds and foxhound-crosses in the U.S. This disease has human health implications; however, there have been no cases of human L. infantum infection acquired in North America to date.
First CasesIn February 2000, a small animal medicine resident, a clinical pathologist, and two fourth-year veterinary students from North Carolina State University (NCSU) diagnosed Leishmania infection in a foxhound, from a hunt club in Dutchess County, New York, that was wintering in the southern U.S. The dog had been taken to NCSU by the manager of the foxhound kennel, who reported that other dogs in the kennel were experiencing a similar, undiagnosed illness. The kennel had been operating as a working foxhound kennel for nearly 100 years.
In August 1999, the foxhounds experienced an unusual illness. The clinical signs included wasting, anorexia, weakness, renal failure, skin lesions, exercise intolerance, and exhaustion. Several of the dogs had been euthanized and necropsied by the kennel’s private practitioner, who observed splenomegaly, hepatomegaly, and renal pathology. The kennel lost 18 dogs to this illness. During October and November 1999, the kennel was losing one dog per week. The dogs had been tested for a variety of tick-borne pathogens in October. The results indicated that they were antibody positive to various Ehrlichia, Babesia, and Rickettsia organisms. The dogs were treated with an insecticide to control the ticks. Various treatments, such as doxycycline and oxytetracycline, were attempted, but did not resolve the clinical illness. Imidocarb treatment (commonly used to treat Babesia infections in dogs) was initiated, but it appeared to be killing some of the hounds and so it was stopped.
At NCSU, Leishmania organisms were identified by direct observation in bone marrow and joint tap samples obtained at necropsy of one dog. Because leishmania is a zoonotic pathogen, Edward Breitschwerdt, professor of Veterinary Internal Medicine at NCSU, reported the diagnosis of canine leishmaniasis to the Center for Disease Control and Prevention (CDC). The CDC began working with the Dutchess County (NY) Department of Health, the Walter Reed Army Institute of Research, the New York State Department of Agriculture, the New York State Department of Health, and the North Carolina State University College of Veterinary Medicine to investigate the outbreak. Serologic testing showed that 46 % of the hounds in the kennel had positive titers to Leishmania. Of the positive dogs, half had died and 13 dogs were ill.
Canine Leishmaniasis in the U.S.
Clinically ill foxhound
Dog, bone marrow. The bone marrow contains hematopoietic precursors and macrophages with numerous intracytoplasmic Leishmania sp. organisms. The elongate
organisms are distinguished by the central round dark basophilic kinetoplast structure
2EEDA/IAT Web-Based Course • DZ Incursions • Visceral Leishmaniasis in Foxhounds • ©2012 CFSPH
The species of leishmania was identified as infantum.
Tests on wild rodents and ticks collected near the kenneled hounds were negative for Leishmania, as were hounds in nearby kennels.
After leishmaniasis was identified in this kennel, the Masters of the Foxhound Association of America issued an official statement on canine leishmaniasis to all member clubs and requested that all hounds be tested.
What is Leishmaniasis?Leishmaniasis is a protozoal parasitic infection caused by many different Leishmania species, including L. infantum, L. donovani, and members of the L. braziliensis L. mexicana and L. tropica complexes. Leishmania organisms are found throughout the tropical and subtropical world, mainly causing disease in humans, dogs and rodents. Cases are rare in most other domesticated animals, although equids and cats are clinically affected occasionally, and there is evidence for subclinical infections (including L. infantum) in cats. L. infantum can infect other species of canids, including foxes and wolves.
Leishmania parasites are usually spread by the bite of an infected female sandfly, a biological vector. Each species of Leishmania is adapted to transmission in certain species of sandflies. Other arthropods including ticks and canine fleas may also act as mechanical vectors. Where sandflies transmit Leishmania spp., ticks and fleas are probably unimportant in the epidemiology of the disease. Dog-to-dog transmission has been reported occasionally in northern Europe and the U.S. In these cases, a dog that had spent time in endemic regions of southern Europe transmitted the disease to a dog that had never traveled to an endemic region. Investigation of canine Leishmania among foxhounds and foxhound-crosses in the U.S. suggests the disease is transmitted dog-to-dog, either horizontally or vertically. Vertical transmission appears to be the primary route of transmission in this situation. Sandflies indigenous to the U.S. have been experimentally infected
Canine Leishmaniasis in the world
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with Leishmania by allowing them to feed on an infected dog. This suggests that vector-borne transmission might have the potential to emerge in the U.S. if the reservoir of infected dogs continues.
In humans, there are different forms of leishmaniasis. The form of the disease and the usual clinical signs vary with the species of Leishmania. In addition to asymptomatic cases, people may develop either cutaneous or visceral leishmaniasis. Cutaneous leishmaniasis ranges from a single open sore, which can leave a discolored scar, to disseminated cutaneous leishmaniasis where lines of nodules, ulcers or other skin lesions can develop along lymphatic vessels, to mucocutaneous leishmaniasis where disfiguring lesions occur around the eyes, nose and mouth. Visceral leishmaniasis in people affects various internal organs such as the spleen, liver, and bone marrow. If left untreated, the visceral form is usually fatal. Approximately 300,000 cases of visceral leishmaniasis and one million cases of cutaneous leishmaniasis occur in humans each year, mainly in parts of Asia, Africa, the Mediterranean, and Central and South America. It is estimated that there are 20,000 to 40,000 human deaths due to leishmaniasis per year. L. infantum usually causes visceral leishmaniasis in people, although some strains have been reported to cause cutaneous leishmaniasis without affecting the internal organs.
In dogs, visceral and cutaneous manifestations may be found either separately or simultaneously. Dogs may also be asymptomatic. Most affected foxhounds suffer from the visceral form of disease with occasional cutaneous manifestations. The clinical signs can include skin lesions, hair loss, epistaxis or other bleeding disorders, wasting, seizures, lymphadenopathy, kidney failure, and swollen limbs and joints. Treatment of visceral leishmaniasis in dogs will diminish clinical signs for years but recrudescence is common. There are new vaccines on the market in Europe and South America.
As previously stated, the possibility that the infection could spread from foxhounds to humans in the U.S. is a concern. Although direct transmission from an infected dog to humans has never been reported, it is theoretically possible. In countries where L. infantum is endemic, infected dogs serve as the primary risk factor for vector-borne zoonotic visceral leishmaniasis in humans. Healthy people are not particularly susceptible to L. infantum and asymptomatic infections with this organism are common. Illness from L. infantum tends to occur mainly in young children or in people who are malnourished or immunosuppressed.
The InvestigationSurveillance for insects or other potential vectors was initiated by the Dutchess County Department of Health in June 2000. Circumstantial evidence suggests the New York foxhounds may have become infected during hunts in other states. Like most hunt organizations, the infected hunt club traveled extensively during the active season, and foxhounds from different packs had opportunities to mix with each other in a number of states. Foxhound Leishmania infections had been previously identified in Oklahoma in 1980, Kansas in 1982, Ohio in 1988, Michigan in 1989, and Texas and Alabama in 1991.
There was no evidence of infections in humans or in pet dogs in the vicinity of any of these previously reported cases. The Foxhound Association recommended that interstate movement of foxhounds be stopped until more information on the extent of this infection and its mode of transmission was available. State public health veterinarians and practicing veterinarians were asked to cooperate in this investigation by acting as local sources of information, facilitating the collection of sera from foxhounds and other potentially exposed dogs, and participating in other aspects of the investigation.
There are about 14,000 registered foxhounds nationwide. Virtually all of these have now been tested once by the CDC’s immunofluorescence assay protocol. In 69 different foxhound kennels in 22 U.S. states and 2 Canadian provinces, at least one seropositive dog was detected. All culture isolates, from multiple states, were typed at the world reference lab in Rome as L. infantum, MON1, a strain that is endemic in the Mediterranean area and causes zoonotic visceral leishmaniasis in that region. Two U.S. isolates and the Spanish MON1 and Israeli MON1 isolates are currently being sequenced at Sanger Institute, Cambridge, England and the data should be available in early 2013. It will be interesting to see how genetically similar or dissimilar these isolates are and what that information adds to the canine visceral leishmaniasis story.
How the disease entered the U.S. may never be known for sure. Cases of leishmaniasis have been seen in the pets of military personnel formerly stationed in foreign locations. Some have suggested that dogs brought into the U.S. from the Middle East may be responsible for the outbreak in foxhounds. On the other hand, given that the incubation period can
4EEDA/IAT Web-Based Course • DZ Incursions • Visceral Leishmaniasis in Foxhounds • ©2012 CFSPH
be as long as seven years and potentially longer, the 1980 cases may have caused all those that followed. A CDC trace back investigation revealed possible connection to dogs acquired from Southern Europe and imported to the U.S. Serology for Leishmania is not required on importation of dogs into the U.S.; therefore, an exact trace back of this epizoonosis may not be possible.
Foxhounds and Visceral LeishmaniasisNo one knows for sure why leishmaniasis in the U.S. appeared in the foxhound breed and continues to affect only this breed. All breeds of dogs are affected in other parts of the world where L. infantum is endemic. Based on genome sequencing, there is no strong evidence for a genetic predisposition among foxhounds. One proposed predisposing factor is the strenuous lifestyle these hunting foxhounds lead. These dogs are the canine equivalent of marathoners (or ultra-marathoners). It is not unusual for these dogs to run 100+ miles in a week and travel for hunts and trials. If nutrition isn’t adequate or there is some other cause of morbidity, they are immunocompromised and susceptible to disease. The other factor that keeps the disease in the breed is that the disease is vertically transmitted from mother to pups. Transplacental transmission from seropositive bitches to their pups occurs with high frequency. Breeding of purebred foxhounds keeps the disease in the foxhound breed. Horizontal transmission between dogs has also been proposed and the aggressive, social nature and environment of foxhounds allows opportunity for transmission through bites or licking. This, however, is uncommon compared to the vertical route of transmission. To date, there is no evidence that these infected foxhounds have transmitted this disease to humans, but given the changeable nature of pathogens, to assume that this will not ever happen is naïve.
Sources of InformationInternet Resources
American Veterinary Medical Association website. Canine leishmaniasis confirmed in 21 states – October 15, 2000. Available at: https://www.avma.org/News/JAVMANews/Pages/s101500f.aspx. Accessed 2012 Centers for Disease Control and Prevention (CDC) http://www.cdc.gov/parasites/leishmaniasis/index.html Companion Animal Parasite Council http://www.capcvet.org/capc-recommendations/canine-leishmaniasis/ Federation of American Scientists http://www.fas.org/ahead/leishmaniasis.htm International Society for Infectious Diseases Subject: PRO/AH> Leishmaniasis, dogs - USA (07) , Published Date: 2000-05-14 23:50:00, Archive Number: 20000514.0754 Subject: PRO/AH/EDR> Leishmaniasis, dogs - USA (Virginia) (02), Published Date: 2001-06-28 23:50:00, Archive Number: 20010628.1228 Available at: http://www.promedmail.org. Accessed 2012. University of Pennsylvania School of Veterinary Medicine website. An uncommon disease in foxhounds. Bellwether, Newsmagazine of the University of Pennsylvania, No. 48,Winter 2001, p21. Available at: http://www.vet.upenn.edu/portals/0/media/bellw48.pdf. Accessible 2012.
References
Alvar, J, et.al. Leishmaniasis worldwide and global estimates of its incidence. PLOS One [online]. 7(5):e35671. doi:10.1371/journal.pone.0035671. Epub 2012 May 31. Available at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035671. Accessed 2012.
Boggiatto, PM, et.al. Transplacental transmission of Leishmania infantum as a means for continued disease incidence in North America. PLOS Neglected Tropical Diseases [online]. April 2011; 5 (4):e1019. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075227/pdf/pntd.0001019.pdf
Duprey, Z., et.al. Canine visceral leishmaniasis. United States and Canada, 2000-2003.. Emerg Infect. Dis 2006;12:440-446.
5EEDA/IAT Web-Based Course • DZ Incursions • Visceral Leishmaniasis in Foxhounds • ©2012 CFSPH
Freeman, KS, et.al. Leishmaniasis in a dog native to Colorado. J Am Vet Med Assoc. 2010; 237(11):1288-1291.
Freeman, KS. Update on the diagnosis and management of Leishmania spp infections in dogs in the United States. Topics in Companion Animal Medicine, 2010, 25(3):149-154.
Monti DJ. Hunters hounded as leishmaniasis is diagnosed in foxhounds. J Am Vet Med Assoc News (online). June 15, 2000. Available at: https://www.avma.org/News/JAVMANews/Pages/s061500a.aspx. Accessed 2012.
Palatnik-de-Sousa.Vaccines for canine leishmaniasis. Frontiers in Immunology (online). 2012, April, doi: 10.3389/fimmu.2012.00069. Available at: http://www.frontiersin.org/Microbial_Immunology/10.3389/fimmu.2012.00069/abstract
Pangrazio, KK, et.al. Tissue distribution of Leishmania chagasi and lesions in transplacentally infected fetuses from symptomatic and asymptomatic naturally infected bitches. Vet Parasitol. 2009;165(3-4):327-31
Petersen, CA, Barr, SC. Canine leishmaniasis in North America: emerging or newly recognized?
Veterinary Clinic North Am Small Anim Pract. 2009 Nov. 39(6):1065-74, vi.
Petersen, CA. Leishmaniasis, an emerging disease found in companion animals in the United States. Topical Review,Topics Companion Animal Med. 2009 Nov; 24(4):182-8.
Petersen, CA. New means of canine leishmaniasis transmission in North America: the possibility of transmission to humans still unknown. Interdiscip Perspect Infect Dis. 2009. Article ID 802712, 5 pages, doi: 10.1155/2009/802712. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695953/ Accessed 2012
Reviewed by: Christine Petersen, DVM, PhD, Assistant Professor, Veterinary Pathology, ISU College of Veterinary Medicine Photo Credits: Dr. Claire Andreasen, Iowa State University, College of Veterinary Medicine, Department of Veterinary Pathology Christine Petersen, DVM, PhD, Assistant Professor, Veterinary Pathology, ISU College of Veterinary Medicine
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