Canine leishmaniosis (CanL) is a major zoonotic disease endemic in more than 70 countries in the world. It is enzootic in regions of southern Europe, Northern Africa, the Middle East, Central Asia, China, South and Central America and has emerged also in dogs in the USA. CanL is also an important concern in non­endemic countries where imported disease constitutes a veterinary and public health problem. Dogs are the main animal reservoir for human visceral leishmaniosis and the disease is usually fatal if not treated in people.^1,2

CanL is a good example of a disease in which infection does not equal clinical illness due to the high prevalence of subclinical infection. This makes CanL a diagnostic challenge for the veterinary practitioner, clinical pathologist and public health official in endemic countries as well as non-endemic regions where imported infection is a concern. The typical history reported by owners of dogs with CanL includes the appearance of skin lesions, ocular abnormalities, or epistaxis.^1-4 These are commonly accompanied by weight loss, exercise intolerance and lethargy. Dogs from all breeds can be infected with leishmaniosis. The age distribution of the disease is bimodal with a peak of prevalence at 2–4 years and a secondary peak from the age of 7 years. The incubation period prior to the appearance of clinical signs may last 3 months up to several years. On physical examination, the main clinical signs associated with CanL are dermal lesions, lymphadenomegaly, splenomegaly, abnormal nails growth (onychogryposis) and poor body condition. Additional findings include: epistaxis, renal failure, decreased appetite, polyuria and polydipsia, vomiting, melena and lameness.^1-4

The main drugs used for treatment of CanL include:

• The pentavalent antimony meglumine antimoniate (Glucanitme®) which selectively inhibits leishmanial glycolysis and fatty acid oxidation.
• Miltefosine (Milteforan®) which is an alkylphosphocholine drug whose antileishmanial mode of action is not entirely understood.
• Allopurinol which acts by inhibiting protein translation through interfering with RNA synthesis.

Despite the World Health Organization’s (WHO) recommendation to reserve anti-leishmanial drugs used for treatment of humans for use in human leishmaniosis and not for veterinary purposes due to potential of drug resistance development,⁵ pentavalent antimonials and miltefosine are often used for treatment of dogs with CanL. Treatment of CanL usually includes a combined regimen with meglumine antimoniate or miltefosine administered for 4 weeks and allopurinol administered simultaneously and then continuously used for long-term therapy.^2-4

Amphotericin B which acts by binding to ergosterol in the parasite’s cell membrane and altering its permeability is also effective against L. infantum but it is highly nephrotoxic. Some other drugs such as marbofloxacin and aminosidine are sometimes used as second line agents.²

Anti-leishmanial treatment often achieves clinical improvement in dogs with leishmaniosis but it is frequently not associated with the elimination of the parasite.^1-4 Treated dogs may remain carriers of the disease, experience clinical relapses and be infectious to sand flies. The successful treatment of CanL is particularly difficult due to the fact that it is lengthy and often does not result in complete elimination of infection, allowing potential relapse of clinical disease and further transmission of infection from treated animals. A clinical staging system for CanL divides the disease into 4 clinical stages based on clinical signs, clinicopathological abnormalities and level of anti-leishmanial antibodies.^3,4 This system is helpful for decisions on the therapy most suitable for each patient and for consideration of a prognosis. The clinical stage may change if the dog deteriorates or improves.

Drug resistance has been widely described in human cutaneous and visceral leishmaniasis. Reports on drug resistance in the canine disease are more scarce. Disease relapse in dogs with CanL during allopurinol treatment has recently been described and associated with allopurinol resistance of L. infantum isolated from relapsed animals. Leishmania infantum strains isolated in culture from relapsed dogs were significantly less susceptible to allopurinol in comparison to isolates from dogs before treatment and those from dogs under treatment with no clinical relapse. Resistance was consistent in three forms of the parasite strains tested including intracellular amastigotes, promastigotes and axenic amastigotes.⁶ These findings indicate that resistance to allopurinol may develop in dogs experiencing clinical disease relapse which may transmit resistant parasite to other dogs and also enhance the danger of transmission the parasite to humans.

In conclusion, the treatment of CanL would benefit from the development of new effective drugs which would be able to eliminate infection from dogs and would not be used for treatment of humans thus reducing the danger of formation of drug resistant parasites that would be passed on to humans.

References

1.  Baneth G, Koutinas AF, Solano-Gallego L, Bourdeau P, Fener L. Canine leishmaniosis - new concepts and insights on an expanding zoonosis: part one. Trends Parasitol. 2008;24:324–330.

2.  Miro G, Cardoso L, Pennisi MG, Olivia G, Baneth G. Canine leishmaniosis - -new concepts and insights on an expanding zoonosis: part two. Trends Parasitol. 2008;24:371–377.

3.  Directions for the diagnosis, clinical staging, treatment and prevention of canine leishmaniosis. Vet Parasitol. 2009;165:1–18.

4.  Parasit Vectors 4:86.

5.  World Health Organization. Control of the Leishmaniasis. Report of a WHO expert committee. World Health Organ Tech Rep Ser. 2010;949:1–186.

6.  Yasur-Landau D, Jaffe CL, David L, Baneth G. Allopurinol resistance in Leishmania infantum from dogs with disease relapse. PLoS Neg/Trop Dis. 2016;10:e0004341.