Leishmaniosis (leishmaniasis) is a vector-borne disease caused by a protozoan parasite that is spread by phlebotomine sand-flies. In Europe, canine leishmaniosis is predominantly caused by Leishmania infantum, although other species (L. tropica, L. major) have occasionally been reported. Leishmania spp. occur and multiply in two well-differentiated forms: intracellular amastigote stages in the vertebrate host and extracellular flagellated promastigote stages in the gut of the phlobotomine vector. The development of the parasite in the vector is temperature-dependent and takes around 7-14 days when average daily temperatures are above 18 °C.

Sand-flies are widespread in the Mediterranean region, Africa and the Middle East, and recent evidence indicates that they may be spreading to new areas as a result of climate change. Maps of current distribution can be accessed through VBORNET. Sand-flies are generally most active at dawn and dusk and require a minimum temperature of 18-22°C during the day; adult sand-flies rest in dark and humid places.

The dog is considered the main reservoir of L. infantum infection and the preferred source of food for phlebotomine sand-flies. The main risks in endemic areas are related to vector exposure and the abundance of reservoir hosts, which include dogs living outdoors, stray dogs, dogs adopted from animal shelters in endemic areas and hunting dogs. Outside endemic areas, the majority of cases occur in imported dogs but non-vectoral transmission through direct contact (bites and wounds), venereal or vertical transmission and via blood transfusion can all enable local foci of infection to be established. There is some evidence of resistance in certain dog breeds (e.g. Ibizian Hound) as well as susceptibility of breeds (e.g. German Shepherd Dog, Rottweiler, Cocker Spaniel, Boxer) to disease development, but no sex- or age-dependent risks have been described.

 

Many other mammalian species can be infected, including foxes, hares and rats. Domestic cats can be infected with Leishmania spp. but clinical signs are rare. Transmission of Leishmania from cats to sand-flies has been demonstrated, which means that they can act as a secondary reservoir of infection.

Image courtesy of M. Saridomihelakis.

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Clinical signs

The incubation period can vary from 3 months to several years and is dependent on the immune response of the individual infected dog. Dogs may present with a wide spectrum of clinical signs and clinicopathological abnormalities, ranging in severity from mild and self-limiting to fatal disease. These include:

  • Local cutaneous lesions (papular or ulcerative lesions called chancres) at the site of the sand-fly bite (often less hairy areas such as the ear pinnae, nose and abdomen) which are self-limiting and often go unnoticed
  • Cutaneous forms of the disease most commonly present as non-pruritic, symmetrical and seborrheic lesions, but papules, ulcers and other skin lesions may be seen
  • Affected dogs may develop enlargement of a single or multiple lymph nodes, reduced appetite and weight loss
  • Other clinical signs may include gastrointestinal disorders (vomiting, diarrhoea, chronic colitis), polyarthritis, glomerulonephritis (polyuria, polydipsia), ocular lesions (blepharitis, conjunctivitis, keratoconjunctivitis, anterior uveitis) and neurological disorders.

However, it should be noted that clinical signs are highly variable and depend on immune responses, disease history and other factors (e.g. other vector-borne diseases such as ehrlichiosis, babesiosis and hepatozoonosis; neoplasia; or immune-mediated diseases).

Following multiplication of the parasites in the dendritic cells and macrophages in the skin, dissemination primarily occurs via the lymphatic and circulatory systems. Following migration, parasites can be found in the skin, lymph nodes, spleen, liver, bone marrow, other internal organs and body fluids.

Diagnosis

A tentative diagnosis can be made based on the clinical signs. However, an accurate diagnosis of canine leishmaniosis requires an integrated approach based on the physical examination, clinicopathological tests and specific assays

  • Direct diagnosis is possible by detecting the amastigote stages of the parasite in Giemsa or Diff-Quik stained smears obtained from the superficial lymph nodes, spleen, liver, bone marrow, other internal organs and, occasionally, body fluids. However, there may be a lot of false-negative results, especially in dogs with a low parasitic load. The sensitivity of parasite detection is lower in skin biopsy samples and is generally reduced in infected but clinically healthy dogs. Sensitivity can be increased with the use of molecular and immunohistochemical techniques
  • Serology is the most commonly used first step, allowing the detection of a specific antibody response in dogs approximately 8-12 weeks after the initial infection. The sensitivity and specificity of serological tests (IFAT and ELISA) is generally good; however, the sensitivity of rapid (qualitative) serological test kits can be variable. High antibody levels are usually associated with clinical disease and high parasite burdens. There is a strong association between clinical signs, high antibody levels and infectivity. However, it is not safe to assume that subclinically affected dogs cannot act as a reservoir of infection
  • Polymerase chain reaction (PCR) assay is both sensitive and specific, and can detect infection earlier than serology. Aspirates from the bone marrow and lymph nodes are most likely to yield positive results in affected dogs, but blood (buffy coat) samples and specimens from other tissues can be used, especially in dogs with a high parasitic burden
  • In dogs with positive serology or PCR assay results for Leishmania, blood samples for renal/liver parameters and urinalysis (urine protein:creatinine ratio) are recommended.

An in-house test kit is now available for the detection of anti-Leishmania infantum kinesin antibodies. However, whilst this test has a reported 98% sensitivity and 100% specificity, the author recommends that until further information is available on the test that infection is confirmed by an external laboratory prior to beginning treatment.

Treatment and prognosis

Drug therapy appears mainly to slow the progression of the infection, decrease infectiveness and improve the clinical signs by reducing the parasitic load. However, even if there is a clinical cure the dog may remain a carrier and therefore a reservoir of infection. No medication is 100% effective in eliminating the parasite and no treatment can guarantee to prevent future transmission.

Before initiating medical management, owners should be informed about the prognosis, costs and the fact that the dog remains infected even if a clinical cure is achieved, and relapses are common.

There are three drugs commonly used for the treatment of leishmaniosis (see BSAVA Small Animal Formulary):

  • Allopurinol (10 mg/kg orally q12h for 6-12 months with meglumine antimonite for 1-2 months or miltefosine for 1 month)
  • Meglumine antimonite (100 mg/kg s.c., i.m., slow i.v. q24h (or divided doses q12h) until clinical remission achieved. Treat for at least 28 days)
  • Miltefosine (2 mg/kg orally q24h for 28 days. It is important that the course is completed and given with allopurinol).

While in non-endemic areas single drug treatments have been used successfully, the most common treatment regimens use a combination of drugs for the first month and then allopurinol, which may need to be continued for life. If there is no clinical improvement after a course of treatment, an alternative drug or a different dosage should be considered. Following completion of the treatment course, it is advisable to monitor the dog for relapse after 3 months and then a 6-monthly intervals.

Symptomatic treatment appropriate to the clinical signs can also be important in managing the disease.

Note: The Leishvet Group has proposed a system that divides the disease into four stages in order to assist the clinician in determining the appropriate therapy and forecasting prognosis. Further information can be found on their website (www.leishvet.org).

Survival depends on the severity of the clinical signs and the owner’s willingness to treat the condition. Reports from France and Portugal indicate that 10-25% of affected dogs are euthanased as a result of the disease, but 30-45% survive for more than 5 years (Mattin et al., 2014).

Prevention

Prevention of phlebotomine sand-fly bites by applying repellents/insecticides to dogs in the form of impregnated collars or spot-on and spray formulations can be useful. Topical insecticides have been shown to be effective in reducing infection in experimental studies, but there is no reliable data on the effectiveness of owner treatment for individual dogs.

  • Topical pyrethroids (± neonicotinoids), which are a component of various sprays and impregnated collars, act as repellents and reduce the number of sand-fly bites. Studies indicate that pyrethroids provide protection and reduce the proportion of dogs which become infected, but they are not 100% effective
  • Deltamethrin impregnated collars can be used. These should be applied at least 1 week before likely exposure to enable protective levels to be achieved.

Vaccination can be provided to dogs over 6 months of age and is based on an initial course of three doses at 3-weekly intervals followed by annual revaccination. However, it should be noted that there is no currently authorized vaccine that is able to confer full protection against infection or disease. Challenge studies indicated that vaccination reduced but did not eliminate the risk of infection. However, vaccination did reduce the parasite load (as determined by quantitative PCR) and clinical signs. It may also reduce infectivity to sand-flies. A combination of vaccination and topical repellents is likely to be most effective, but there are no studies to demonstrate this.

To help prevent disease, dogs should be housed, especially at dawn and dusk, between April and November, when the sand-flies are most likely to bite. For kennelled dogs in endemic areas, strict measures to control vectors and vector-borne diseases should be maintained.

To avoid an extension of endemic areas, Leishmania-infected dogs should not be translocated to non-endemic areas where phlebotomine sand-flies (or other vectors) may be present. Testing dogs before their movement from an endemic to a non-endemic area is of limited value as it can take several months for seroconversion to occur following exposure. Testing and treatment of dogs prior to their movement from an endemic to a non-endemic area does not appear to be an efficient or realistic option to mitigate the possibility of introduction of leishmaniosis.

Monitoring

Recommendations on monitoring disease have been developed in areas where leishmaniosis is prevalent. Although they may not always be appropriate for animals that have been imported into non-endemic regions, the recommendations provide a starting point for discussion. Serological testing can be useful for monitoring infected dogs for changes in disease severity and response to treatment. It is important to check whether the animal has been vaccinated against L. infantum when interpreting serology.

Condition of animal Parameter Frequency
Exposed but not showing clinical signs Clinical examination, serology 2-4 months after exposure
Seropositive but no clinical signs Clinical examination, serology, haemotology, biochemistry, urinalysis Every 3-6 months
PCR positive/serongative Clinical examination, serology, haemotology, biochemistry, urinalysis Every 3-6 months
Clinically affected Clinical examination, haemotology, biochemistry, urinalysis
Serology
At the start of treatment to provide baseline, after first month of treatment and every 3-4 months during first year
After 6 months of treatment, then every 6-12 months
Clinically recovered Clinical examination
Haemotology/biochemistry/urinalysis
Serology
Every 6-12 months
Every 6-12 months
At least once year

Public health implications

Leishmania can be transmitted to humans and is an important disease, especially in poorer parts of South America, East Africa and Southeast Asia. In Europe, the majority of human cases are associated with immunosuppressive diseases such as human immunodeficiency virus (HIV). The major route of transmission is via sand-fly bite; transmission from infected dogs is thought to be extremely uncommon. A high proportion of human infections are asymptomatic; however, the World Health Organization (WHO) estimates that 20,000-30,000 people die annually from this disease.

References and further reading

Belo VS, Struchiner CJ, Werneck GL et al. (2013) A systematic review and meta-analysis of the factors associated with Leishmania infantum infection in dogs in Brazil. Veterinary Parasitology 195(1), 1-13
ESCCAP Guidelines on Control of Vector-Borne Diseases in Dogs and Cats (2012)
Mattin M, Brodbelt D, Wylie C, Antoñanzas MC and Gallego LS (2014) Data collection to characterise the impact of canine leishmaniosis and modelling of the role of animals in spreading Leishmania infantum within the European Union. European Food Safety Authority [doi: 10.2903/sp.efsa.2014.EN-466]
Mattin MJ, Solano-Gallego L, Dhollander S, Afonso A and Brodbelt DC (2014) The frequency and distribution of canine leishmaniosis diagnosed by veterinary practitioners in Europe. The Veterinary Journal 200(3), 410-419
Miró G, Oliva G, Cruz I et al. (2009) Multicentric, controlled clinical study to evaluate effectiveness and safety of miltefosine and allopurinol for canine leishmaniosis. Veterinary Dermatology 20, 397-404
Pennisi M-G, Cardoso L, Baneth G et al. (2015) Leishvet update and recommendations on feline leishmaniosis. Parasites and Vectors 8, 302
Peixoto HM, Oliveira MRF and Romero GAS (2015) Serological diagnosis of canine visceral leishmaniasis in Brazil: systematic review and meta‐analysis. Tropical Medicine & International Health 20(3), 334-352
Ramsey IK (2014) BSAVA Small Animal Formulary, 8th edition. BSAVA Publications, Gloucester
Roura X, Fondati A, Lubas G et al. (2013) Prognosis and monitoring of leishmaniasis in dogs: a working group report. The Veterinary Journal 198(1), 43-47
Solano-Gallego L, Koutinas A, Miró G et al. (2009) Directions for the diagnosis, clinical staging, treatment and prevention of canine leishmaniosis. Veterinary Parasitology 165(1), 1-18
Solano-Gallego L, Miró G, Koutinas A et al. (2011) LeishVet guidelines for the practical management of canine leishmaniosis. Parasites and Vectors 4(1), 86

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