Canine leishmania

Cutaneous signs of leishmania, phto by
Merck Veterinary Manual

CLINICAL SIGNS AND PRESENTATIONS

Leishmaniasis is a disease caused by protozoan parasites of Leishmania spp, transmitted to humans and animals by vectors. Canines are susceptible to acquire a visceral (L. infantum) and cutaneous form (L. panamensis, L. braziliensis). Some dogs or some breeds seem to be more resistant to the development of the disease.

It is endemic in several countries in the Mediterranean countries, where dogs are the main reservoir for Leishmania infantum, the causative agent of the visceral form in humans.

The disease is transmitted to mammals through female sand fly bites naturally infected, Phlebotomus, in Europe, Asia and Africa. In domestic environment felines, equines, bovines, birds, rabbits, and rodents are also susceptible. Epidemiologically and clinically, the importance lies in the canine as main reservoir.

Two presentation are described: 

1. patients were the cellular immune response dominates and there is a low production of antibodies are associated with the resolution of symptoms but they continue to be positive, or be asymptomatic in up to 80% in some areas.

2. patients where there is a high production of antibodies, developing the disease progressively, forming immune complexes in different organs, which makes the treatment at the clinic more difficult. 

Symptoms

◦ local or generalized lymphadenopathy, 
◦ cutaneous injuries (ulcers, bedsores), alopecia, dermatitis (exfoliative, nodular, pustular), ulcers at the scrotal level, onychogryphosis 
◦ progressive wasting (even when the patient has not lost appetite or the food is of good quality), muscular atrophy 
◦ eye injury (uveitis, conjunctivitis, keratoconjunctivitis, blepharitis) 
◦ kidney failures occur in almost all canines: glomerulonephritis, due to the deposit of immune complexes in the glomerular capillary walls, causing irreversible damage to the nephrone, resulting in kidney failure and azotemia
◦ diarrhea, hematuria, limps and fever in some cases 
◦ joint injuries such as polyarthritis 
◦ splenomegaly, epistaxis: death can occur after an uncontrollable loss of blood, immune-mediated erythrolysis, disseminated intravascular coagulation associated to the hemorrhages, platelet consumption and coagulation factors

Clinical symptoms in dogs, by www.intechopen.com

DISEASE FACTORS 

The parasite completes the cycle in two hosts, the vector and the reservoir. Promastigotes mature into their infective form in the vector and are then transmitted to the reservoirs. A severe inflammatory chain is initiated because in the closest regional lymphatic gland, dentridic cells present parasite antigens to the lymphocytes. Initially, Th1 lymphocytes predominate when the immune response is cellular, there are low antibody titers and it seems that the infection is self-limiting. The dog is apparently healthy. 

Th2 lymphocytes predominate in the severe stage of the disease, where promastigotes are engulfed by macrophages, neutrophines and killer cells, to destroy them. However, within the macrophages, promastigotes are transformed into amastigotes, they begin to multiply and break the membrane of the macrophage, scattering themselves and migrating to various organs. In this stage there are high antibodies, the cellular immunity drops and there is a high population of parasites in the entire organism. This triggers a migration of complex Antigen-Antibodies that causes all the symptoms.

Transmission

Blood transfusions, placenta and venereal transmission. Bytes of infected canines and the transmission through ticks and fleas are not considered as transmission mechanisms.

INITIAL BIOSECURITY PROCEDURES

The World Health Organization (WHO) has classified leishmaniasis in category I as an emerging disease without control. For cases compatible with visceral leishmaniasis euthanasia is recommended since no other treatment is available and because of the role that the canine has as a source of parasites to the vector. For cases compatible with cutaneous stains the treatment is symptomatic.

CONFIRMATION OF THE DIAGNOSIS

◦ Haematology: normocytic, normochromic non regenerative anemia, and leukopenia can be observed 
◦ Biochemistry: increase in ALT and AST and, with more frequency, an increase in the urea and creatinine levels. 
◦ Urinalysis: proteinuria, casts in the sediment indicative of glomerulonephritis. 
◦ Cytology and staining of the bone marrow, poplyteal lymph nodes, or a subcutaneous portion of the injuries or the ulcers are also fast and effective tools to identify positive dogs in cases where the patient shows evident clinical signs and signs compatible with the disease. The presence of one amastigote inside the macrophages is considered a diagnosis of infection. If the cytology is negative, the serology is the tool to choose to confirm the antibody titers. 
◦ PCR and snap tests.   

MANAGEMENT OF CLINICAL DISEASE

◦ Meglumine antimoniate, 100 mg/kg/day subcutaneus (Glucantime injection for dogs 1.5g/5ml, Merial) with allopurinol (10-20 mg/kg/ day orraly for 6-12 months) has been established as the most used and efficient protocol.

◦ Amphotericin B

◦ Miltefosine, (Milteforan 20mg-ml, oral suspension, Virbac) is recommended 2 mg/kg/day orally during 28 days with allopurinol (10 mg/kg/day orally for 6-12 months). Miltefosine increases the activity of amphotericin B and meglumine antimoniate. 

◦ Domperidone, 0.5 mg/ kg/day for 30 days during times when the activity of the vectors increases is available for the treatment and prevention of leishmaniasis in Europe. It is taken by mouth, inexpensive and can be used in patients with kidney failure (Gomez Ochoa et al., 2009). The study demonstrated that domperidone makes the dog 7 times less susceptible to infection while the vaccine makes them 4 times less susceptible. Likewise, domperidone proved to be efficient in the reduction of antileishmania antibodies during the first stages of the infection, thus possibly reducing the risk of deposit of immune complexes and controlling the subclinical infection.

◦ They will not be cured even though they clinically show an improvement in the clinical signs, relapses are constant, infected and asymptomatic dogs can exist that can act as reservoirs, infecting the vectors. 

PREVENTION STRATEGIES

◦ Some countries consider euthanasia as the best option in canines to avoid the installation and propagation of the disease. Its failures as an eradication method are the non-acceptance by the public, low sensibility to the diagnostic tests, late detection of the disease and replacement of the sacrificed canine by a susceptible one.The animal has the right not to suffer. It will be necessary to evaluate the benefits of this treatment versus euthanasia and the transmission of the disease in the population. Owners must be conscious of hygiene rules and precautions that must be taken, the cost of the treatment, its success, the use or destination of the animal. The veterinary surgeon must consider the public and animal health, and the potential of an epizootic outbreak. 
◦ Pets travelling to endemic areas were recommended to use Advantix pipettes prior to their arrival
◦ Pets travelling out of endemic areas were recommended being tested of leismaniasis.
◦ External use repellents against the vector in pipettes with imidacloprid and permethrin (Advantix spot-on, Bayer), pyrethroids and insecticides in kennels, mosquito nets, permethrin and deltramethrin based ectoparasiticides collars (Scalibor, collar, Intervet/Schering-Plough Animal Health) 
◦ healthy and immunocompetent dogs with updated sanitary schemes and right nutrition are less susceptible.
◦ Vaccines approved by the EU:
- Letifend (laboratories leti) For active immunisation of non-infected dogs from 6 months of age to reduce the risk of developing an active infection and/or clinical disease after exposure to Leishmania infantum.The vaccine is given from 6 months of age as a single injection under the skin. A ‘booster’ injection should be given yearly. Protection starts four weeks after vaccination and lasts one year.
- Canileish (Virbac) is used in dogs from six months of age to reduce the risk of developing an active infection and clinical disease after contact with Leishmania infantum. The vaccine is given as three injections, three weeks apart, under the skin. Afterwards, a single ‘booster’ should be given yearly to maintain the vaccine’s effect.

AUTHOR’S CASES

In my 8 years as a veterinary surgeon in South Spain, an average of 2 dogs per week were confirmed with leishmaniasis through an in-house snap test, with a peak in the spring and the autumn. A most typical presentation wound be any dog exposed to phlebotomus in the past three months, living in or near houses with gardens and ponds (damp and warn environment), with recurrent dermatitis and non-healing pustules in tip of ears, conjunctiva, nostrils and joints (sorebeds), several recent episodes of gastroenteritis or “sensitive stomach”, bleeding disorders (epistaxis, photo bellow), and nail overgrowth.

Once the snap test was read as positive, next step would be sending a blood sample to an external lab for antibodies titter valuation. Every three months this titters would be re-evaluated. Haematology and biochemistry profiles would be performed, and initial treatment would depend on the other symptoms presented.

Milteforan and allopurinol, as described above, was advice as best optional treatment in all cases, as it proved to have less side effects in the patients as well as being less aggressive to the internal organs. In dogs presenting a very poor condition or renal parameters very high, milteforan was strongly advised. When cost was an issue, glucantime and allopurinol was recommended. 

All dogs were advised to be vaccinated after 6 months of age.

All dogs were advice to use advantix pipettes, after noticing that Scalibor collars did not seem either protect the back rear of large dogs or last as mosquitoes repellent for longer than 4 months. 

Pets re-homed abroad would be tested for leishmaniasis, erlichiosis and heartworm disease, and the results registered in their passports.

No quarantine were applied.

References:

Rosa M. Reguera, Miguel Morán Yolanda Pérez-Pertejo, Carlos García-Estrada, Rafael Balaña-Fouce, (2016) ‘Current Status of Prevention and Treatment of Canine Leishmaniasis’, Veterinary Parasitology, August 2016, volumen 227, pages 98-114

Xavier Roura, A Fondati, G. Libas, L Gradoni, M Maroli, G Oliva, S Paltrinieri, A Zatelli, E Zini (2013) ‘Prognosis and monitoring of leishmaninasis in dogs: a working group report’, The Veterinary Journal, October 2013, vol 198 (1), pages 43-47

C Maia, L Cardoso (2015)‘Spread of Leishmania infantum in Europe with dog travelling, Veterinary Parasitology, 2015, volume 213, pages 2-11

‘Letifend canine leishmaniasis vaccine (recombinant protein)’, European public assessment report (EPAR) . Last updated in February 2016. Available at http://ec.europa.eu/health/documents/community-register/html/v195.htm (accessed on 6th January 2017)