Leishmaniosis is caused by protozoal parasites of the genus Leishmania. In dogs, key clinical signs range from localized cutaneous lesions to systemic disease. Diagnosis is often based on serological testing, with quantitative tests such as immunofluorescence assays or ELISA. Treatment options include combination use of allopurinol with miltefosine or allopurinol with meglumine antimoniate.
Leishmaniosis is caused by protozoal parasites of the genus Leishmania. Leishmaniosis is a major zoonosis.
Among nonhuman animals, most clinical cases are reported in dogs. Cats, horses, and other mammals can also be infected (also see Leishmaniosis in Cats).
Leishmaniosis is also called leishmaniasis, especially when referring to cases in humans; however, the terms are sometimes used interchangeably.
Etiology and Pathophysiology of Leishmaniosis in Dogs
The etiological agents of leishmaniosis are protozoal parasites of the genus Leishmania (order Trypanosomatida, family Trypanosomatidae, subfamily Englishman). More than 23 Leishmania species have been described, and most are zoonotic.
The most important Leishmania parasite to affect domestic animals is Leishmania infantum. Dogs are the main reservoir host for L infantum (1).
On the basis of genetic sequencing, Leishmania chagasi has been synonymized with L infantum; however, antigenic differences might mark these as distinct strains (2).
Leishmania braziliensis and related species cause mucocutaneous leishmaniosis.
Pathogenesis of Leishmaniosis in Dogs
Leishmania is a diphasic parasite that completes its life cycle in two hosts: a sand fly that harbors the flagellated extracellular promastigote form, and a mammal in which the intracellular amastigote parasite form develops.
Dogs are thought to be most commonly infected by Leishmania promastigotes deposited into the skin via the bites of infected sand flies. Promastigotes invade host macrophages and replicate as intracellular amastigotes (3) (see L infantum image).
Courtesy of Dr. Gad Baneth.
The incubation period of leishmaniosis can last months to years, during which the parasite disseminates throughout the host’s body, primarily to hemolymphatic system organs.
Immune responses mounted at the time of L infantum infection and thereafter appear to be the most important factor in determining whether a subclinical chronic infection will progress to clinical illness (4).
Age, breed, host genetics, nutrition, concurrent infectious and noninfectious diseases, immunosuppressive conditions or treatments, and other factors can also influence the progression of a subclinical Leishmania infection to one with clinical signs and/or clinicopathological abnormalities of disease.
Epidemiology of Leishmaniosis in Dogs
Prevalence and Geographic Distribution of Leishmaniosis in Dogs
Leishmaniosis is endemic in > 89 countries; it is prevalent in Europe, Africa, Asia, and South and Central America. Leishmaniosis is vertically transmitted in dogs in the US and other parts of the world. It is also of concern in nonendemic countries, where imported disease is a veterinary and public health concern (5).
L braziliensis is widespread in regions of South America and might geographically overlap with L infantum.
In areas where leishmaniosis is endemic, the percentage of dogs carrying infection is much higher than that of dogs demonstrating disease. Several studies performed in endemic areas have shown that infection rates usually vary from 5 to 30% in the dog population, but they can reach > 60% in highly endemic areas (6, 7, 8, 9). However, approximately only 10% of infected dogs manifest clinical signs (10, 11).
Transmission of Leishmaniosis in Dogs
Two principal routes of leishmaniosis transmission in dogs have been confirmed: vector-borne transmission by the bites of female phlebotomine sand flies and vertical transmission from dam to pup. Transmission via sand flies is a complex process that requires special adaptation between the sand fly host and the particular Leishmania species transmitted (12, 13).
Pearls & Pitfalls
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There are numerous species of sand flies, only a minority of which are competent vectors of Leishmania. Dogs with or without clinical signs of leishmaniosis are infectious to sand flies and can transmit Leishmania parasites.
Congenital vertical transmission of L infantum infection from an infected dam to its offspring has been reported.
Transmission by transfusion of blood products from infected dogs has been shown to cause L infantum infection in recipients. Direct dog-to-dog transmission by contact has been reported as a likely mode of transmission in several cases in which household fighting or contact with diseased dogs is the only known contact (14).
Clinical Findings of Leishmaniosis in Dogs
A wide range of clinical signs and clinicopathological abnormalities are common in leishmaniosis in dogs.
In dogs, clinical manifestations include cutaneous, mucocutaneous, and ocular lesions; systemic clinical signs; and neurological signs. Ocular and cutaneous and mucocutaneous lesions can develop with or without other signs of systemic disease. The disease can be fatal when severe chronic renal disease develops.
The typical history reported by owners of dogs with leishmaniosis includes the appearance of skin lesions, ocular abnormalities, and other signs. These clinical signs are frequently accompanied by pale mucous membranes, weight loss, exercise intolerance, and lethargy.
The main physical examination findings of leishmaniosis in dogs include dermal abnormalities, lymphadenomegaly, ocular disease, splenomegaly, and hepatomegaly.
Other clinical findings of leishmaniosis in dogs, besides dermal abnormalities, include polyuria/polydipsia due to kidney disease, epistaxis, vomiting, diarrhea, ocular abnormalities, and lameness resulting from joint, muscle, or bone lesions. Neurological and neuromuscular abnormalities, as well as vascular disorders, have also been documented with leishmaniosis in dogs.
Dermal lesions associated with leishmaniosis in dogs include exfoliative dermatitis with or without alopecia (see cutaneous signs image), erosive-ulcerative dermatitis, nodular dermatitis, papular dermatitis, pustular dermatitis, and nail abnormalities such as onychogryphosis. Cutaneous lesions can be generalized or localized, most commonly over the face, ears, and limbs.
Courtesy of Veterinary Dermatological Service, Veterinary Teaching Hospital at Autonomous University of Barcelona (HCV-UAB).
Mucocutaneous and mucosal ulcerative or nodular lesions (oral, genital, and nasal) are also encountered in dogs with leishmaniosis.
A mild form of papular dermatitis has been reported in dogs without other signs of disease or clinicopathological abnormalities.
Ocular or periocular lesions include blepharitis (exfoliative, ulcerative, or nodular); conjunctivitis (nodular) and keratoconjunctivitis (either common or sicca); and anterior uveitis.
Clinicopathological abnormalities are also very common in L infantum infection in dogs.
Hematologic findings include mild to moderate normocytic, normochromic, nonregenerative anemia; and either leukocytosis (neutrophilia) or leukopenia (lymphopenia and neutropenia; see Leukogram Abnormalities in Animals). Thrombocytopenia is less common.
Disease is associated with a marked antibody response that does not confer protection. Therefore, the most consistent serum biochemical abnormalities in dogs with leishmaniosis are serum hyperproteinemia with hyperglobulinemia (polyclonal beta- and/or gammaglobulinemia) and hypoalbuminemia, frequently expressed as a decreased albumin:globulin ratio. Marked hyperglobulinemia with no apparent cause in dogs from Leishmania-endemic regions is compatible with leishmaniosis.
Some renal pathological changes are present in most dogs with leishmaniosis; however, they might not be clinically apparent. Grossly increased liver enzyme activity or renal azotemia is found in only a minority of Leishmania-infected dogs. Subsequent renal failure due to immune complex glomerulonephritis can eventually develop and is believed to be the main cause of death. Proteinuria should be evaluated and kidney disease staged via measurement of a urine protein:creatinine ratio (see Chronic Kidney Disease), among other renal and urinary markers.
To facilitate standardization of treatment and epidemiological and clinical studies, clinical staging schemes for leishmaniosis in dogs have been developed (15).
Lesions of Leishmaniosis in Dogs
The typical histopathological finding in leishmaniosis in dogs is granulomatous and lymphoplasmacytic inflammation associated with a variable number of Leishmania amastigotes within macrophages.
Protective immunity against Leishmania parasites is mediated through CD4+type 1 helper T cells and activation of a complex cascade of cytokine mediators such as IFN-gamma. High levels of circulating immune complexes and antinuclear antibodies can be detected in dogs with leishmaniosis, and immune complexes are deposited in the kidneys, blood vessels, and joints as infection progresses.
Glomerulonephritis is a hallmark of leishmaniosis.
Diagnosis of Leishmaniosis in Dogs
Clinicopathological findings
Serological testing
Cytological and histological examination
PCR assay
Diagnosing leishmaniosis in dogs is difficult and requires an integrated approach that includes both clinicopathological evaluation and specific laboratory tests (15).
A detailed medical history of the patient (including a travel history to endemic areas) should be obtained and a thorough physical examination performed.
Diagnostic tests for leishmaniosis in dogs include a CBC, biochemical profile, urinalysis, and one or more specific tests to confirm infection.
Quantitative serological testing is best for diagnosis of leishmaniosis and particularly sensitive when compatible clinical signs are present (16). Antibody levels above diagnostic cutoffs are found in most affected dogs.
Various quantitative serological methods to detect anti-Leishmania antibodies have been developed, including indirect immunofluorescence assays, ELISA, and direct agglutination assays. Purified recombinant antigens such as rK39 are also used to detect leishmaniosis in dogs and humans in several rapid lateral flow formats as screening assays. However, these rapid serological assays have variable diagnostic performance.
Serological cross-reactivity with different Leishmania species and trypanosomes can be found in regions where Trypanosoma infection is prevalent, particularly with Trypanosoma cruziwhere it is endemic (much of South America, Central America, Mexico, and the southern US) (17).
Leishmania amastigotes can be demonstrated by cytological evaluation of aspirates from lymph nodes, spleen, skin lesions, liver, bone marrow, joints, or other biological fluids stained with Giemsa stain or a quick commercial stain (18). Because the similar parasite T cruzi also has an amastigote form with a kinetoplastid, in regions where T cruzi is endemic, visualization of amastigotes does not necessarily confirm a diagnosis of Leishmania infection.
Detection of Leishmania amastigotes by cytological evaluation is sometimes unrewarding because of a low number of detectable parasites, even in dogs with full-blown disease.
Leishmania parasites can also be viewed in histological formalin-fixed, paraffin-embedded biopsy sections of the skin or other infected organs. Identification of parasites within tissue macrophages can be difficult in histological specimens; immunolabeling with immunohistochemical staining can verify the presence of Leishmania in the tissue.
Detecting Leishmania infection in subclinically affected dogs for purposes such as importation to nonendemic countries or use as blood donors might require quantitative serological and PCR techniques.
Detection of parasite-specific DNA by PCR assay enables sensitive and specific diagnosis of infection. Several assays with various target sequences using genomic or kinetoplast DNA (kDNA) have been developed for leishmaniosis in dogs. PCR assays can be performed on DNA extracted from tissues or blood, or even from histological specimens.
Assays based on kDNA are the most sensitive for direct detection of leishmaniosis in infected tissues; however, these sequences have been shown to have variability over time. Bone marrow, lymph node, or spleen samples are superior to blood for most current PCR techniques (19).
Treatment of Leishmaniosis in Dogs
Antiprotozoal agents
Immunotherapy
Antiprotozoal Agents for Treatment of Leishmaniosis in Dogs
Treatment of leishmaniosis in dogs frequently does not provide a sterilizing cure. Treated dogs can remain carriers of infection and can relapse.
The main protocol for treating leishmaniosis in dogs includes inhibition of parasite phosphofructokinase metabolism with N-methylglucamine antimoniate (50–100 mg/kg, SC, every 24 hours for 4–6 weeks). N-methylglucamine antimoniate can cause local pain and inflammation at the injection site, rarely pancreatitis, and potentially nephrotoxicosis. Recrudescence or relapse can occur after 6–12 months.
Miltefosine disrupts the calcium homeostasis of the parasite and inhibits cytochrome c oxidase, causing apoptosis-like cell death. Miltefosine (2 mg/kg, PO, every 12 hours for 28 days) can be combined with allopurinol (10 mg/kg, PO, every 12 hours, for 6–12 months or longer as needed). Side effects include dysorexia, vomiting, and diarrhea. Recrudescence and relapse can occur after 4–6 months.
Allopurinol can be used as a single therapeutic agent (10 mg/kg, PO, every 12 hours for 6–12 months or longer as needed). It is able to disrupt RNA synthesis and interfere with protein synthesis. Side effects include xanthine crystalluria and urolithiasis, renal mineralization, and nephrolithiasis. Recrudescence and relapse can occur after 4–6 months.
If meglumine antimoniate or miltefosine in combination with allopurinol is not available, paromomycin (4 mg/kg, SC, every 12 hours for 3 weeks) can be administered. Paromomycin is an inhibitor of bacterial protein synthesis through irreversible binding to the 30S ribosomal subunit in mitochondria. Paromomycin can cause nephrotoxicosis and ototoxicosis. Recrudescence or relapse can occur after 3–4 months.
Dogs treated for leishmaniosis can remain infectious to sand flies and perpetuate transmission of the disease. Stopping allopurinol treatment is recommended only when clinical signs disappear; hematologic, serum biochemical, and urinalysis abnormalities resolve; and the animal becomes seronegative or low seropositive by a quantitative serological test.
In very susceptible sick dogs, treatment can be extremely long, even lifelong. However, adverse effects of treatment might be frequent and should be monitored.
Immunotherapy for Treatment of Leishmaniosis in Dogs
The outcome of Leishmania infection in a dog depends largely on the dog’s immune response. Therefore, treatment that can enhance the immune system's function could provide an alternative means to combating infection.
The only commercially available immunotherapeutic drug specifically for treatment of leishmaniosis in dogs is domperidone. Licensed as an immunotherapeutic drug for leishmaniosis in dogs in Europe, domperidone (0.5 mg/kg, PO, every 24 hours for 4 weeks) is a dopaminergic D2 receptor antagonist that can potentiate the immune response (20). This immunotherapeutic drug can be administered in noninfected dogs to prevent infection, and in healthy infected dogs to prevent disease development. Domperidone is also available for veterinary use in the US; however, in the US it is not licensed for this purpose.
Dietary nucleotides and the dietary supplement "active hexose correlated compound" are marketed for treatment of dogs with leishmaniosis. These nucleotides are not licensed drugs for the treatment of leishmaniosis; instead, they are food supplements that can strengthen the immune system and boost the innate and adaptive immune responses. Active hexose correlated compound seems useful to lower disease progression in healthy infected dogs, and it can also be recommended to supplement the standard treatment in sick dogs (21, 22).
Prevention of Leishmaniosis in Dogs
Specific repellent topical insecticides effectively decrease sand fly bites and transmission of L infantum infection (see the table Insecticides With Anti–Sand Fly Efficacy). Application of protective insecticides is recommended for dogs in Leishmania-endemic areas, dogs traveling to endemic areas, and infected dogs (to decrease potential transmission).
Insecticides With Anti–Sand Fly Efficacy
Active Ingredient(s) | Dose (range) | Application | Protection onset | Duration of Protection |
|---|---|---|---|---|
Deltamethrin | 40 mg/g | Collar | 7 days | 1 yr |
Flumethrin, imidacloprid | 56 mg/g | Collar | Unknown | 8 mo |
Permethrin | 47.6 mg/kg | Spot-on | 24–48 h | 2 wk |
Not applicable | Spray | Instant | 2–3 d | |
Permethrin, dinotefuran, pyriproxyfen | 46.6–158.8 mg/kg | Spot-on | 24–48 h | 4 wk |
Permethrin, fipronil | 50.5–160 mg/kg | Spot-on | 24–48 h | 4 wk |
Permethrin, imidacloprid | 50–125 mg/kg | Spot-on | 24–48 h | 3–4 wk |
Permethrin, indoxacarb | 48–96 mg/kg | Spot-on | 24–48 h | 3–4 wk |
Adapted from Miró G, Petersen C, Cardoso L, et al. Novel areas for prevention and control of canine leishmaniosis. Trends Parasitol. 2017;33(9)718-730. doi:10.1016/j.pt.2017.05.005 | ||||
Insecticides with anti–sand fly efficacy include pyrethroids (deltamethrin, flumethrin, permethrin), imidacloprid, dinotefuran, pyriproxyfen, fipronil, and indoxacarb. A deltamethrin-impregnated collar and a spot-on formulation of permethrin and imidacloprid have been shown to confer protection against sand fly bites.
In the US, insecticides are regulated by the EPA and must be used consistently with their registered labeling.
Purified-fraction commercial vaccines against leishmaniosis in dogs are marketed in Europe and Brazil (see the table Vaccines Against Leishmaniosis in Dogs), and other vaccines are under development. However, no vaccines against leishmaniosis are licensed for use in the US, and if administered, they must be used under USDA permit.
Vaccines Against Leishmaniosis in Dogs
Vaccine Composition | Vaccination Protocol | Antibody Kinetics in Initial Vaccination | Vaccine-Associated Interference With Serological Testing | Availability |
|---|---|---|---|---|
Recombinant chimeric protein Q No adjuvant | Initial SC dose Annual reinforcement | Peak: 14 days after initial vaccination Duration: basal levels at 180 days | No detection of vaccine antibodies by quantitative tests or rapid tests | Europe |
Recombinant A2 antigen of Leishmania donovani Saponin adjuvant | Three initial SC doses, with 21 days between consecutive doses Annual reinforcement | Peak: 21 days after second initial dose Duration: decrease after 6 months | Detection of vaccine antibodies with ELISA | Brazil |
DNA plasmid containing LACK gene No adjuvant | Two primary vaccination doses (intranasal),15-day interval One booster every 6 months | Not described | No detection of vaccine antibodies | Europe |
Adapted from Solano-Gallego L, Cardoso L, Pennisi MG, et al. Diagnostic challenges in the era of canine Leishmania infantum vaccines. Trends Parasitol. 2017; 33(9)706-717. doi:10.1016/j.pt.2017.06.004 | ||||
Domperidone (0.5 mg/kg, PO, every 24 hours for 4 weeks every 4 months), which is available in several European countries, is approved for prevention of leishmaniosis in dogs.
Zoonotic Risk of Leishmaniosis in Dogs
Human visceral leishmaniasis caused by L infantum is a serious public health problem in areas where leishmaniosis is endemic in dogs, and dogs remain the main reservoir of infection. Malnutrition and other immune-altering diseases, including human immunodeficiency virus (HIV) infection, are recognized as key risk factors for leishmaniasis in humans and might explain why this disease is opportunistic.
HIV and leishmaniasis coinfection in humans has been reported in > 80 countries worldwide. Control over leishmaniasis in humans is established when there is a sufficient CD4+ T-cell population after treatment with combination antiretroviral therapy.
Efforts to limit infection with Leishmania in dogs and humans in endemic areas focus on disrupting the transmission of infection through sand fly control measures and on preventing canine infection at the population level.
Key Points
Leishmaniosis is an important zoonosis, particularly in South America and the Mediterranean basin, as well as in North Africa and the Middle East. Dogs are still thought to be a predominant reservoir.
Where disease is not found to be endemic in humans, dogs can still become infected by mating with infected animals imported from endemic areas or by traveling to endemic areas without protection against sand fly bites.
Prevention using appropriate insecticides and vaccination where available is best. Treatment is unlikely to lead to sterile cure, and clinical signs can recrudesce in months to years after treatment.
For More Information
WHO: Leishmaniasis
CDC: Leishmaniasis
Also see pet owner content regarding leishmaniosis in dogs.
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