LeishVet guidelines for the practical management of canine leishmaniosis
© Solano-Gallego et al; licensee BioMed Central Ltd. 2011
Received: 25 April 2011
Accepted: 20 May 2011
Published: 20 May 2011
The LeishVet group has formed recommendations designed primarily to help the veterinary clinician in the management of canine leishmaniosis. The complexity of this zoonotic infection and the wide range of its clinical manifestations, from inapparent infection to severe disease, make the management of canine leishmaniosis challenging. The recommendations were constructed by combining a comprehensive review of evidence-based studies, extensive clinical experience and critical consensus opinion discussions. The guidelines presented here in a short version with graphical topic displays suggest standardized and rational approaches to the diagnosis, treatment, follow-up, control and prevention of canine leishmaniosis. A staging system that divides the disease into four stages is aimed at assisting the clinician in determining the appropriate therapy, forecasting prognosis, and implementing follow-up steps required for the management of the leishmaniosis patient.
Canine leishmaniosis (CanL) due to Leishmania infantum is a major global zoonosis potentially fatal to humans and dogs, which comprise the main reservoir of infection to humans . CanL is endemic in more than 70 countries in the world. It is present in regions of southern Europe, Africa, Asia, South and Central America  and has been reported also in the United States of America (USA) . It is also an important concern in non-endemic countries where imported sick or infected dogs constitute a veterinary and public health problem .
CanL is manifested by a broad spectrum of clinical signs and degrees of severity, and there is insufficient scientific agreement on the management of this disease . LeishVet is a group of veterinary scientists from academic institutes in Europe and the Mediterranean basin with a main clinical and scientific interest in CanL. The main goal of LeishVet is to develop consensus recommendations that would represent the most current understanding of L. infantum infection in dogs based on recent evidence-based literature and clinical experience . The objective of these guidelines is to help practitioners in the clinical management of CanL with emphasis on diagnosis, clinical staging, treatment, clinical monitoring, prognosis and prevention.
Life cycle and transmission
Distribution and epidemiology
Leishmania infantum frequently follows an insidious and chronic pattern of infection . Therefore, CanL is a disease in which infection does not equal clinical illness resulting in a high prevalence of subclinical infection [2, 26].
Several predisposing factors for the development of disease have been described including breed, age and genetic background. Some dog breeds such as the Boxer, Cocker Spaniel, Rottweiler and German Shepherd seem to be more susceptible to the development of disease [29, 30], while others such as the Ibizian Hound rarely develop clinical signs of CanL . The Slc11c1 (Solute carrier family 11 member a1) gene, formerly named N-RAMPI, and certain alleles of the MHC II genes have been associated with susceptibility to CanL [32, 33]. Age seems to be an important factor. The distribution of the disease is bimodal, with the highest prevalence reported in dogs younger than 3 years and older than 8 years [34, 35].
Clinical manifestations and laboratory abnormalities
Clinical manifestations and laboratory abnormalities found in canine leishmaniosis due to L. infantum
○ Generalized lymphadenomegaly
○ Loss of body weight
○ Decreased or increased appetite
○ Mucous membranes pallor
○ Polyuria and polydypsia
○ Diarrhea (including chronic colitis)
Serum proteins and electrophoretogram
Polyclonal beta and/or gammaglobulinemia
○ Decreased albumin/globulin ratio
○ Non-pruritic exfoliative dermatitis with or without alopecia
○ Erosive-ulcerative dermatitis
○ Nodular dermatitis
○ Papular dermatitis
○ Pustular dermatitis
○ Mild to moderate non-regenerative anemia
○ Leukocytosis or leukopenia
○ Impaired secondary hemostasis and fibrinolysis
○ Blepharitis (exfoliative, ulcerative, or nodular) and conjunctivitis (nodular)
○ Keratoconjunctivitis, either common or sicca
○ Anterior uveitis/Endophtalmitis
○ Mild to severe proteinuria
○ Renal azotemia
○ Elevated liver enzyme activities
○ Mucocutaneous and mucosal ulcerative or nodular lesions (oral, genital and nasal)
○ Lameness (erosive or non-erosive polyarthritis, osteomyelitis, polymyositis)
○ Atrophic masticatory myositis
○ Vascular disorders (systemic vasculitis, arterial thromboembolism)
○ Neurological disorders
Cytological and histopathological patterns suggestive of canine L. infantum infection found in organs or body fluids.
Pathological findings in organs or body fluids
✔ Macrophagic inflammation (granulomatous)
✔ Neutrophilic-macrophagic inflammation (pyogranulomatous)
✔ Lymphoplasmacytic inflammation
✔ Reactive hyperplasia in lymphoid organs
✔ No evidence or variable numbers of intracellular or extracellular Leishmania amastigotes
The diagnosis of CanL is complex as the clinical spectrum is broad and the range of clinicopathological abnormalities based on at least a complete blood count (CBC), biochemical profile and urinalysis can be both wide and non-specific. A thorough clinicopathological diagnostic approach needs to be adapted for each patient when assessing the suspicion of this disease. In addition, dogs with leishmaniosis might be co-infected with other vector borne diseases or suffering from other concomitant infectious or non-infectious diseases making the differential diagnoses more complicated and diverse. Therefore, based on the clinicopathological problem list, a differential diagnosis and specific diagnostic approach would be made for each patient.
Advantages and disadvantages of common diagnostic methods for the detection of L. infantum infection in dogs.
• Determination of antibody level which is essential for the diagnosis and establishing a prognosis
• Does not detect the actual presence of the Leishmania parasite
• Serocrossreactions with trypanosomes
• Rapid in-clinic test
• Provides only positive or negative result
• Variable sensitivities and performance with risk of false negatives
• A positive result needs to be further evaluated by a quantitative serology
Determines the antibody level
• High antibodies levels in the presence of compatible clinical signs and/or clinicopathological abnormalities are conclusive of clinical leishmaniosis
• Performance and accuracy of cut-off will depend on the laboratory
• Differences between laboratories and poor standardization of techniques
• Low antibody levels will require further work-up
Permits direct detection of the parasite itself and the type of pathological findings:
- Pathological findings suspicious of infection
- Allows exclusion of other differential diagnoses
- Rapid and non invasive (cytology)
• Low sensitivity for the detection of Leishmania amastigotes in tissues or body fluids
• Requires the performance of other diagnostic tests such as immunohistochemistry and/or PCR when parasites are not visualized
• Does not reveal the immunological status of the dog
• Needs expertise
• Allows the detection of leishmanial DNA
• High sensitivity (kDNA) and specificity
• Parasitic load quantification (if Real time-PCR)
• False positive results possible due to DNA contamination
• Different standardization and techniques used by different diagnostic laboratories
• Does not reveal immunological status
• It cannot be performed as the sole diagnostic technique for the confirmation of the disease because a positive result confirms Leishmania infection but not disease
• Permits the isolation of Leishmania parasites
• Facilitates the isoenzymatic identification of the parasite
• Time-consuming and laborious diagnostic technique
• It can require one month to provide a result
• Performed only in research laboratories
Clinical staging, treatment and prognosis
Clinical staging of canine leishmaniosis based on serological status, clinical signs, laboratory findings, and type of therapy and prognosis for each stage 
Stage I Mild disease
Negative to low positive antibody levels
Dogs with mild clinical signs such as peripheral lymphadenomegaly, or papular dermatitis
Usually no clinicopathological abnormalities observed
Normal renal profile: creatinine < 1.4 mg/dl; non-proteinuric: UPC < 0.5
Scientific neglect/allopurinol or meglumine antimoniate or miltefosine/allopurinol + meglumine antimoniate or allopurinol + miltefosine**
Stage II Moderate disease
Low to high positive antibody levels
Dogs, which apart from the signs listed in stage I, may present: diffuse or symmetrical cutaneous lesions such as exfoliative dermatitis/onychogryphosis, ulcerations (planum nasale, footpads, bony prominences, mucocutaneous junctions), anorexia, weight loss, fever, and epistaxis
Clinicopathological abnormalities such as mild non-regenerative anemia, hyperglobulinemia, hypoalbuminemia, serum hyperviscosity syndrome
a) Normal renal profile: creatinine < 1.4 mg/dl; non-proteinuric: UPC < 0.5
b) Creatinine <1.4 mg/dl; UPC = 0.5-1
Allopurinol + meglumine antimoniate or allopurinol+ miltefosine
Good to guarded
Stage III Severe disease
Medium to high positive antibody levels
Dogs, which apart from the signs listed in stages I and II, may present signs originating from immune-complex lesions: vasculitis, arthritis, uveitis and glomerulonephritis.
Clinicopathological abnormalities listed in stage II
Chronic kidney disease (CKD) IRIS stage I with UPC > 1 or stage II (creatinine 1.4-2 mg/dl) 
Allopurinol + meglumine antimoniate or allopurinol + miltefosine
Follow IRIS guidelines for CKD 
Guarded to poor
Stage IV Very severe disease
Medium to high positive antibody levels
Dogs with clinical signs listed in stage III. Pulmonary thromboembolism, or nephrotic syndrome and end stage renal disease
Clinicopathological abnormalities listed in stage II
CKD IRIS stage III (creatinine 2-5 mg/dl) and stage IV (creatinine > 5 mg/dl)  Nephrotic syndrome: marked proteinuria UPC > 5
Follow IRIS guidelines for CKD 
Current treatment protocols for canine leishmaniosis 
Main side effects
75-100 mg/kg once a day or 40-75 mg/kg twice a day for 4 weeks, S.C.**
2 mg/kg/once a day for 28 days P.O.
10 mg/kg twice a day for at least 6-12 months P.O.
The clinical response to treatment of sick dogs can vary from poor to good depending on their overall initial clinicopathological status and their specific response to therapy. Dogs with renal insufficiency are expected to have a lower recovery rate in comparison to those without kidney compromise or only mild proteinuria. Therapy with antileishmanial drugs often leads to clinical cure  although treated dogs may continue to harbour the parasite and be infectious to sand flies, but to a lesser extent than pre-treatment [52, 55–57].
Treatment of canine leishmaniosis - recommended monitoring of clinicopathological parameters and serology including frequency of follow up .
Clinical history and complete physical examination
Routine laboratory tests:
Complete CBC, biochemical profile, serum electrophoresis (optional) and complete urinalysis including UPC in proteinuric dogs.
After the first month of treatment and then every 3-4 months during the first year. Later on, if the dog is fully recovered clinically with treatment, a recheck would be recommended every 6 months or once a year.
Not before 6 months after initial treatment and every 6 months or once a year thereafter.
Real time PCR
Can optionally be carried out at the same time as serology. The full usefulness of this assay for follow up during treatment is currently undetermined.
The presence of complete physical and clinicopathological recovery evaluated by a thorough physical examination, CBC, full biochemistry panel and urinalysis.
A marked decrease of antibody levels (to negative or borderline by a quantitative serological assay).
In addition, allopurinol might be discontinued if it is not possible to control or decrease the xanthinuria with low purine diets or by reducing the drug's dosage, to avoid the risk of urolithiasis, if massive xanthine crystalluria is present .
Management of clinically healthy infected dogs in endemic areas
The management of clinically healthy infected dogs in areas where CanL is endemic is of great importance for practitioners.
The presence of Leishmania DNA in the blood or other tissues of clinically healthy dogs living in endemic areas indicates that these dogs harbour infection , but they may never develop clinical disease . In contrast, a high positive antibody titer may indicate that an infected dog is heading towards the development of a widespread infection and future development of clinical disease . Therefore, we recommend using serology alone or the combination of serology with PCR for screening healthy dogs. It is recommended to avoid screening clinically healthy dogs only by PCR.
They are scheduled to travel or be exported to non-endemic areas (Figure 14)
They serve as blood donors (Figure 2)
Their owners wish to have them monitored at least every 12 months for early detection of infection and the potential to develop disease.
PCR should be used for the second above indication and as an ancillary test for the first and third above indications.
The management of a clinically healthy seropositive dog and a clinically healthy seronegative and PCR-positive dog is summarized in Figure 14.
Current preventative measures are mainly based on the use of veterinary registered products containing synthetic pyrethroids, permethrin, or deltamethrin with a repellent effect against sand flies whose efficacy has been demonstrated both experimentally [61–63] and in field studies [64–68]. These products are available in spot on formulation or in a collar form and they reduce the risk of new infections and the biting of sand flies on already infected dogs [64–68]. Other measures useful in the prevention of sand fly bites include [69, 70]: 1) keeping the dog indoors during the sand fly season from dusk to dawn; 2) reducing microhabitats favourable to sand flies such as piles of wood and stones in the vicinity of the house and in other locations where dogs spend time; 3) usage of indoor insecticide treatment .
Permethrin/Imidacloprid spot on formulation: Treatment provides repellent (anti feeding) activity against sand flies (P. perniciosus) for three weeks . Repeat administration every 3 weeks. It should be applied at least 2 days before travelling
Deltamethrin collars: Control of feeding by phlebotomine sand flies (P. perniciosus) for a period of 5-6 months . Replace collar every 5-6 months. It should be applied at least 1-2 weeks before travelling.
Veterinarians and dog owners are advised to carefully check the product's label recommendations and follow the manufacturer's instructions for the correct application and frequency of reapplication. Client education on the maintenance of an appropriate insecticide  throughout the period of sand fly activity in the Mediterranean basin (April-November) is also crucial for the protection of dogs .
Purified Leishmania fraction vaccines appear currently to be the most effective and promising vaccines for dogs. These include the ''fucose mannose ligand'' (FML)-based vaccine [72, 73] and an excreted/secreted antigen purified from specific-medium culture supernatant of L. infantum based vaccine . The FML-based vaccine is currently available commercially in Brazil. The same vaccine has also been proposed as a transmission-blocking vaccine . Recently, another vaccine which contains the recombinant A2 protein and saponin as adjuvant has also been approved in Brazil . In Europe, a different vaccine based on cultured L. infantum purified excreted/secreted antigens has been approved for vaccination of dogs .
The future for CanL control should be an integrated approach to prevention including vaccination against L. infantum with an effective canine vaccine and the use of long-acting topical insecticide applications. A vaccine would prevent the establishment of infection introduced by the bites of those sand flies that escape the insecticide effect .
Public health considerations
In Southern Europe, human visceral leishmaniosis caused by L. infantum is a zoonotic disease that affects young children or adults suffering from the Acquired Immune Deficiency Syndrome (AIDS) or immunosuppressive conditions [77, 78]. Dogs are considered the most important peridomestic reservoir of L. infantum infection for humans. However, the ownership of an infected dog does not appear to greatly increase the risk of disease in the family when transmission is already present in the region .
The complexity of CanL and the wide range of its clinical manifestations, from inapparent infection to severe disease, make the management of CanL challenging. Diagnosis is performed based on clinicopathological manifestations and by confirmation of infection using mainly serological and molecular techniques. A staging system that divides the disease into four stages is aimed at assisting the clinician in determining the appropriate therapy, forecasting prognosis, and implementing follow-up steps required for the management of the leishmaniosis patient. Prevention should be an integrated approach including vaccination against L. infantum with an effective canine vaccine and the application of a topical insecticide.
List of abbreviations
Acquired Immune Deficiency Syndrome
Complete blood count
Chronic kidney disease)
Enzyme-linked immunosorbent assay
Fucose mannose ligand
Immunofluorescence antibody test
International Renal Interest Society
- MHC II:
Major histocompatibility complex type II
Natural Resistance-associated Macrophage Protein one
Polymerase chain reaction
Solute carrier family 11 member a1
Urinary protein creatinine ratio
United States of America
The authors would like to acknowledge Dr. Norbert Mencke and the kind support of Bayer Animal Health GmbH. The authors would like to thank scientists, human physicians and veterinarians that have advanced the understanding of canine leishmaniosis. Publication of this manuscript has been sponsored by Bayer Animal Health GmbH. All authors are members of LeishVet. LeishVet address: Dpto. Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Spain e-mail: email@example.com
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