Canine leishmaniasis

Canine leishmaniasis (LEESH-ma-NIGH-ah-sis) is a zoonotic disease (see human leishmaniasis) caused by Leishmania parasites transmitted by the bite of an infected phlebotomine sandfly. Canine leishmaniasis was first identified in Europe in 1903, and in 1940, 40% of all dogs in Rome were determined to be positive for leishmaniasis.[1] Traditionally thought of as a disease only found near the Mediterranean basin, 2008 research claims new findings are evidence that canine leishmaniasis is currently expanding in continental climate areas of northwestern Italy, far from the recognized disease-endemic areas along the Mediterranean coasts.[2] Cases of leishmaniasis began appearing in North America in 2000,[3] and, as of 2008, Leishmania-positive foxhounds have been reported in 22 U.S. states and two Canadian provinces.[4]

A dog displaying a typical clinical picture of visceral leishmaniasis

Forms and symptoms

Cutaneous

  • Alopecia
  • Skin lesions
  • Ulcerative or exfoliative dermatitis

Visceral

  • Epistaxis (nose bleeds)
  • Kidney failure > increased urination and drinking
  • Ocular signs
  • Progressive loss of weight with decreased appetite
  • Swollen lymphnodes

Cause

Numerous strains and subgenus strains of Leishmania exist; with sandfly genome projects still underway, strains are still being discovered.[5]

In the Old World, leishmaniasis transmitted by sandflies of the genus Phlebotomus documented in dogs are:

New World leishmaniasis strains are spread by Lutzomyia; however, research speculates the North American sandfly could be capable of spreading, but this is to date unconfirmed. Dogs are known reservoirs of L. infantum, and the spread of disease from dog to dog has been confirmed in the United States.

  • Suspected causes of canine visceral leishmaniasis are geographic variants of the Leishmania donovani complex, including[7] L. infantum, L. chagasi and L. donovani.

The Mexicana (L. mexicana, L. amazonensis, L. venezuelensis, and L. pifanoi) and Viannia (L. braziliensis, L. guyanensis, L. panamensis and L. peruviana) strains are not commonly found in dogs. Subgenus Viannia strains are found only in Central and South America, all of which cause leishmaniasis in humans.[8]

Transmission

Traditionally, canine transmission is directly from sandfly to dog. Cases in the United States have proven L. infantum transmission from dog to dog by direct contamination with blood and secretions, as well as transplacentally from an infected bitch to her pups.[9] This mode of transmission seems to be unique to the L. infantum Mon1 strain found in the United States. Although in utero transmission is likely the predominant method of disease spread amount the L. infantum Mon1 strain, it is still a viable parasite (has not lost virulence factors associated with sandfly-uptake) which can be transmitted via sandfly bite.[10] A Brazilian study of 63 puppies from 18 L. donovani-infected parents found no evidence of congential or transplacental infection.[4]

Diagnosis

In the United States, certain breed clubs are strongly recommending screening for Leishmania, especially in imported breeding stock from endemic locations. For reasons yet unidentified The Foxhound and Neapolitan Mastiff seem to be predisposed or at higher risk for disease.[3][11] The Italian Spinone Club of America is also requesting all breeders and owners to submit samples for testing; the club reported 150 Spinone Italiano dogs have tested positive in the United States.[12]

In the United States, the following veterinary colleges and government bodies assist with testing and treatment of Leishmania-positive dogs:

  • Centers for Disease Control and Prevention on Leishmaniasis in dogs [13]
  • Iowa State University Department of Pathology[14]
  • North Carolina State University College of Veterinary Medicine

Diagnostic testing includes molecular biology and genetic techniques which provide high accuracy and high sensitivity/specificity. The most commonly employed methods in medical laboratories include Enzyme-Linked Immunosorbent Assays, aka ELISA (among other serological assays) and DNA amplification via Polymerase Chain Reaction (PCR). The Polymerase Chain Reaction (PCR) method for detecting Leishmania DNA is a highly sensitive and specific test, producing accurate results in a relatively short amount of time. A study completed in which Foxhounds were tested using PCR showed that approximately 20% of the tested dogs were positive for leishmaniasis; the same population tested with serological/antibody assays showed only 5% positive.[15]

Diagnosis can be complicated by false positives caused by the leptospirosis vaccine and false negatives caused by testing methods lacking sufficient sensitivity.

Prevention

In areas where the known vector is a sandfly, deltamethrin collars worn by the dogs has been proven to be 86% effective.[16] The sandfly is most active at dusk and dawn; keeping dogs indoors during those peak times will help minimize exposure.

Unfortunately, there is no one answer for leishmaniasis prevention, nor will one vaccine cover multiple species. "Different virulence factors have been identified for distinct Leishmania species, and there are profound differences in the immune mechanisms that mediate susceptibility/resistance to infection and in the pathology associated with disease."[17]

In 2003, Fort Dodge Wyeth released the Leshmune vaccine in Brazil for L. donovani (also referred to as kala-azar in Brazil).[18] Studies indicated up to 87% protection.[19] Most common side effects from the vaccine have been noted as anorexia and local swelling.[19] The president of the Brazil Regional Council of Veterinary Medicine, Marcia Villa, warned since vaccinated dogs develop antibodies, they can be difficult to distinguish from asymptomatic, infected dogs.[20] Studies also indicate the Leshmune vaccine may be reliable in treating L. chagasi, and a possible treatment for dogs already infected with L. donovani.[21][22]

Treatment

Currently, no cure exists for canine leishmaniasis, but various treatment options are available in different countries. Treatment is best coordinated with veterinary research hospitals. Treatment does vary by geographic area, strain of infection and exhibited symptoms. Dogs can be asymptomatic for years. Most common treatments include:

L. donovani

  • Antimony resistant so amphotericin B is recommended

L. infantum[23]

There have been no documented cases of leishmaniasis transmission from dogs to humans.

Research directions

In the United States, research examining the Foxhound and Neapolitan Mastiff is scheduled to continue into 2011 at the University of Iowa. The goals of this project are to screen for the presence of the Leishmania parasite DNA and to be a stepping stone to future research of T-cell function with the hopes of understanding canine leishmaniasis as a model for better understanding human leishmaniasis.

  • Foxhound submissions forms[24]
  • Neapolitan Mastiff submission forms[25]

Also in the United States, the CDC is monitoring Italian Spinones, with no end date indicated on sample submissions.

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References

  1. Dereure J., Pratlong F., Dedet, J.P (1999) Geographical distribution and the identification of parasites causing canine leishmaniasis in the Mediterranean Basin. Canine leishmaniasis: an update. Proceedings of the International Canine Leishmaniasis Forum. Barcelona, Spain
  2. Ferroglio E, Maroli M, Gastaldo S, Mignone W, Rossi L (October 2005). "Canine leishmaniasis, Italy". Emerging Infect. Dis. 11 (10): 1618–20. doi:10.3201/eid1110.040966. PMC 3366729. PMID 16318709.
  3. Monti, Dean (June 2000). "Hunters hounded as leishmaniasis is diagnosed in Foxhounds". J Am Vet Med Assoc. 216 (12): 1887, 1890. PMID 10863579.
  4. Rosypal, Alexa. (2005) Characterization of Canine Leishmaniasis in the United States: Pathogenesis, Immunological Responses, and Transmission of an American Isolate of Leishmania infantum. Veterinary Clinics of North America Small Animal Practice Journal. Blacksburg, VA.
  5. http://www.genome.gov/Pages/Research/Sequencing/SeqProposals/SandFliesSeq.pdf
  6. Nawaratna S.S.K.; et al. (2009). "Cutaneous leishmaniasis in Sri Lanka: a study of possible animal reservoirs". International Journal of Infectious Diseases. 13 (4): 513–7. doi:10.1016/j.ijid.2008.08.023. PMID 19095480.
  7. Duprey Z.H.; et al. (2006). "Canine visceral leishmaniasis, United States and Canada, 2000-2003". Emerging Infect. Dis. 12 (3): 440–6. doi:10.3201/eid1203.050811. PMC 3291440. PMID 16704782.
  8. "Pathogens". Archived from the original on 24 July 2009. Retrieved 30 April 2006.
  9. "Companion Animal Parasite Council". Capcvet.org. Archived from the original on 2012-02-13. Retrieved 2012-10-04.
  10. Schaut, Robert G.; Robles-Murguia, Maricela; Juelsgaard, Rachel; Esch, Kevin J.; Bartholomay, Lyric C.; Ramalho-Ortigao, Marcelo; Petersen, Christine A. (2015-12-01). "Vectorborne Transmission of Leishmania infantum from Hounds, United States". Emerging Infectious Diseases. 21 (12): 2209–2212. doi:10.3201/eid2112.141167. ISSN 1080-6059. PMC 4672406. PMID 26583260.
  11. Petersen CHF paper 2008
  12. "Spinone Club of America Health Information - Spinoni Italiani". Archived from the original on 16 January 2008. Retrieved 30 April 2006.
  13. "Centers for Disease Control and Prevention: Leishmaniasis in Dogs".
  14. "Office of Biotechnology: Iowa State University". Biotech.iastate.edu. Archived from the original on 2013-10-16. Retrieved 2012-10-04.
  15. Petersen paper find notes
  16. Reithinger R, Teodoro U, Davies CR (2001). "Topical insecticide treatments to protect dogs from sand fly vectors of leishmaniasis". Emerging Infect. Dis. 7 (5): 872–6. doi:10.3201/eid0705.010516. PMC 2631889. PMID 11747701.
  17. McMahon-Pratt D, Alexander J (October 2004). "Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease?". Immunol. Rev. 201: 206–24. doi:10.1111/j.0105-2896.2004.00190.x. PMID 15361243.
  18. Nogueira FS, Moreira MA, Borja-Cabrera GP, et al. (September 2005). "Leishmune vaccine blocks the transmission of canine visceral leishmaniasis: absence of Leishmania parasites in blood, skin and lymph nodes of vaccinated exposed dogs". Vaccine. 23 (40): 4805–10. doi:10.1016/j.vaccine.2005.05.011. PMID 16011864.
  19. Parra LE, Borja-Cabrera GP, Santos FN, Souza LO, Palatnik-de-Sousa CB, Menz I (March 2007). "Safety trial using the Leishmune vaccine against canine visceral leishmaniasis in Brazil". Vaccine. 25 (12): 2180–6. doi:10.1016/j.vaccine.2006.11.057. PMID 17239495.
  20. Moreno, Saulo. 2004, October. Brazzil Magazine. Authorized use of Leishmania Vaccine. Made in Brazil. Avail online: http://www.brazzilmag.com/content/view/579/41/
  21. de Andrade RA, Reis AB, Gontijo CM, et al. (March 2007). "Clinical value of anti-Leishmania (Leishmania) chagasi IgG titers detected by flow cytometry to distinguish infected from vaccinated dogs". Vet. Immunol. Immunopathol. 116 (1–2): 85–97. doi:10.1016/j.vetimm.2007.01.002. PMID 17287029.
  22. Santos FN, Borja-Cabrera GP, Miyashiro LM, et al. (August 2007). "Immunotherapy against experimental canine visceral leishmaniasis with the saponin enriched-Leishmune vaccine". Vaccine. 25 (33): 6176–90. doi:10.1016/j.vaccine.2007.06.005. PMC 7115527. PMID 17630055.
  23. http://asmcourse.ivic.ve/articulos/urbina/urbina3.pdf%5B%5D
  24. "Christine A. Petersen | Iowa State University". Vetmed.iastate.edu. 2010-06-05. Archived from the original on 2012-11-14. Retrieved 2012-10-04.
  25. "Neapolitan Mastiff Study". Everythingneo.com. 2009-02-26. Archived from the original on 2012-09-15. Retrieved 2012-10-04.
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