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CANINE LEISHMANIOSIS (CanL)

LeishVet brief information for


the practicing veterinarian

LEISHVET GUIDELINES FOR THE PRACTICAL MANAGEMENT OF CANINE LEISHMANIOSIS (CanL)

Content
DIAGNOSIS 3
CLINICAL STAGING

THERAPY 9

Monitoring 10

PREVENTION 12
REFERENCES 13
ABOUT LEISHVET

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LEISHVET MEMBERS

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DIAGNOSIS

DIAGNOSIS
Diagnosis is performed based on physical and clinicopathological manifestations and
by confirmation of infection, using mainly serological and molecular techniques.
Main purposes for the diagnosis of Leishmania infantum infection:

Confirm presence of the disease.

Screen clinically healthy dogs living in or travelling to endemic areas.

Screen blood donors.

Diagnostic Approach
Dog with clinical signs and/or clinicopathological abnormalities compatible with CanL

HIGH

Confirmed
CanL

POSITIVE

Quantitative serology

LOW

Cytological/histological
evaluation

YES

Leishmania amastigotes

POSITIVE

NO
PCR

NEGATIVE
High
suspicion
of CanL

NEGATIVE

Consider
other
diagnoses

LEISHVET GUIDELINES FOR THE PRACTICAL MANAGEMENT OF CANINE LEISHMANIOSIS (CanL)

Clinical manifestations and laboratory abnormalities found


Clinical manifestations

Laboratory abnormalities

General

Serum proteins and electrophoretogram

Generalized lymphadenomegaly
Loss of body weight
Decreased or increased appetite
Lethargy
Pallor mucous membranes
Splenomegaly
Polyuria and polydypsia
Fever
Vomiting
Diarrhea (including chronic colitis)

Hyperglobulinemia
(Polyclonal beta- and/or gammaglobulinemia)
Hypoalbuminemia
Decreased albumin/globulin ratio

Cutaneous

CBC/Hemostasis

Non-pruritic exfoliative dermatitis


with or without alopecia
Erosive-ulcerative dermatitis
Nodular dermatitis
Papular dermatitis
Pustular dermatitis
Onychogryphosis

M
 ild to moderate non-regenerative
anemia
Leukocytosis or leukopenia
Thrombocytopathy
Thrombocytopenia
Impaired secondary hemostasis and
fibrinolysis

Ocular

Biochemical profile/urinalysis

Blepharitis (exfoliative, ulcerative,


or nodular) and conjunctivitis (nodular)
K eratoconjunctivitis (either common or sicca)
Anterior uveitis/endophthalmitis

Mild to severe proteinuria


Renal azotemia
Elevated liver enzyme activities

Other
M
 ucocutaneous and mucosal ulcerative or
nodular lesions (oral, genital, and nasal)
Epistaxis
Lameness (erosive or non-erosive poly
arthritis, osteomyelitis, polymyositis)
Atrophic masticatory myositis
Vascular disorders (systemic vasculitis, arterial
thromboembolism)
Neurological disorders

Sand fly (Phlebotomus spp.)


feeding on a human finger

( Photo by R. Pospischil, Monheim,


Germany)

DIAGNOSIS

in CanL due to infection with L. infantum


Infected but healthy versus sick dogs
Dogs with clinical leishmaniosis are those presenting suggestive clinical signs and/or clinicopatho
A 
logical abnormalities, and having a confirmed L. infantum infection.

Dogs with subclinical infection (or clinically healthy but infected dogs) are those that present neither
B 

clinical signs on physical examination nor clinicopathological abnormalities on routine laboratory tests
(CBC, biochemical profile and urinalysis) but have a confirmed L. infantum infection.

Diagnostic methods

A
B
C

Parasitological: cytology/histology, immunohistochemistry and culture.


Molecular: conventional, nested and real-time polymerase chain reaction (PCR).
Serological: quantitative (IFAT and ELISA) and qualitative (rapid tests).

samples and techniques to be used for PCR


Samples
recommended (more sensitive tissues):
bone marrow
lymph node

spleen

skin

conjunctiva

B Samples not recommended (less sensitive samples): blood, buffy coat, and urine.
More sensitive technique: real-time PCR.
C 

Intracellular Leishmania
infantum amastigotes
within a dogs macrophage
(bone marrow cytology;
Giemsa-stained blood
smear)( A. F. Koutinas,
Thessaloniki, Greece)

LEISHVET GUIDELINES FOR THE PRACTICAL MANAGEMENT OF CANINE LEISHMANIOSIS (CanL)

CLINICAL STAGING
A system that divides the disease into four stages and is aimed at assisting the clinician in determining
the appropriate therapy, forecasting prognosis, and implementing follow-up steps required for the
management of the canine leishmaniosis patient.

Clinical staging of CanL based on serological status, clinical signs,


laboratory findings, and type of therapy and prognosis for each stage

Clinical stages

Serology*

Clinical signs

Stage I

Negative to low positive


antibody levels

Mild peripheral lymphadenomegaly


papular dermatitis

Low to high positive


antibody levels

Stage I signs plus: diffuse or symmetrical


cutaneous lesions such as exfoliative dermatitis/onychogryphosis, ulcerations (planum
nasale, footpads, bony prominences, mucocutaneous junctions), anorexia, weight loss,
fever, and epistaxis

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

Medium to high positive


antibody levels

Dogs with clinical signs listed in stage III:


pulmonary thromboembolism, or nephrotic
syndrome and end-stage renal disease

Mild disease

Stage II
Moderate disease

Stage III
Severe disease

Stage IV
Very severe disease

* Dogs with negative to medium positive antibody levels should be confirmed as infected by other diagnostic techniques such as
cytology, histology, immunohistochemistry, or PCR. High levels of antibodies defined as a three- tofourfold elevation above the
cut off level of a well-established reference laboratory are conclusive of a diagnosis of CanL.

CLINICAL STAGING

Sand fly
(Phlebotomus spp.)

Laboratory findings

Therapy

Prognosis

Usually no clinicopathological abnormalities observed

Good

Normal renal profile: creatinine <1.4 mg/dl; nonproteinuric: UPC < 0.5

Treat with anti-Leishmania short-term


therapy or monitor
without treatment**

Clinicopathological abnormalities such as mild


non-regenerative anemia, hyperglobulinemia,
hypoalbuminemia, serum hyperviscosity syndrome

Allopurinol + meglumine
antimoniate or
allopurinol + miltefosine

Good to guarded

Allopurinol + meglumine
antimoniate or
allopurinol + miltefosine

Guarded to poor

Substage
a) Normal renal profile: creatinine < 1.4 mg/dl;
non-proteinuric: UPC < 0.5

b) Creatinine <1.4 mg/dl; UPC=0.51

Clinicopathological abnormalities listed in stage II:


Chronic kidney disease (CKD) IRIS stage I with UPC>1
or stage II (creatinine 1.42 mg/dl)

Follow IRIS1
guidelines for CKD
Clinicopathological abnormalities listed in stage II:

Allopurinol (alone)

CKD IRIS stage III (creatinine 25 mg/dl) and


stage IV (creatinine > 5 mg/dl)

Follow IRIS
guidelines for CKD

Poor

Nephrotic syndrome: marked proteinuria UPC>5


1

IRIS: International Renal Interest Society (www.iris-kidney.com)

** Initiation of any therapeutic intervention is dependent on the individual case. Dogs in stage I are likely to require less prolonged
treatment with one or two combined drugs or alternatively monitoring with no treatment. However, there is limited information
on dogs in this stage and, therefore, treatment options remain to be defined.

LEISHVET GUIDELINES FOR THE PRACTICAL MANAGEMENT OF CANINE LEISHMANIOSIS (CanL)

Some clinical signs found in CanL

A
B
C
D
E

Epistaxis
Bilateral uveitis and corneal opacity
Purulent conjunctivitis and blepharitis
Exfoliative alopecia in the rear leg and popliteal lymphadenomegaly
Marked cachexia and generalized exfoliative alopecia

THERAPY
Drugs

Dosages

Main side effects

Meglumine antimoniate*

75100 mg/kg once a day or


4075 mg/kg twice a day for
4 weeks S.C.**

Potential nephrotoxicity
C
 utaneous abscesses/
cellulitis

Miltefosine*

2 mg/kg once a day for 28 days


P.O.

Vomiting
Diarrhea

Allopurinol

10 mg/kg twice a day for at least


612 months P.O.

Xanthine urolithiasis

THERAPY

Current treatment protocols for CanL

P.O.: per os; S.C.: subcutaneous


* Registered for veterinary use in some European countries; both drugs are commonly recommended in combination with allopurinol.
** Recommended dosages out of label but according to pharmacokinetic and clinical studies in dogs. Treatment prolongation by
23 weeks may be considered if patient improvement is insufficient.
Disclaimer: Information given here on drugs and dosages are based on a consensus of clinical and scientific experience by the
LeishVet members. These recommendations have been published in scientific peer-reviewed journals. Veterinary practitioners
are requested to check with product leaflets and product registrations in their related country prior to any product selection and
initiation of treatment.

LEISHVET GUIDELINES FOR THE PRACTICAL MANAGEMENT OF CANINE LEISHMANIOSIS (CanL)

Monitoring
Recommended monitoring of clinicopathological parameters and serology
during and after treatment of CanL
Parameter

Frequency

Clinical and laboratory:


Anamnesis (clinical history)
Complete physical examination
CBC
Biochemical profiles
Serum electrophoresis (optional)
Urinalysis (incl. UPC in case of a
proteinuric patient)

After the 1st month of treatment


Every 34 months during the 1st year
After clinical recovery: 6-monthly recheck

Serology*:

First testing 6 months after onset of treatment


Every 6 months or at least once a year

Real-time PCR

Current scientific status: not recommended unless


combined with serology

* Possible serological findings following therapy:


Some dogs present a significant decrease in antibody levels (more than a twofold dilutions difference between the first and the
following samples) associated with clinical improvement within 6 months to 1 year of treatment. Other dogs might not have a
decrease in antibody levels despite clinical improvement. In contrast, a marked increase of antibody levels (more than two-fold
elevation between monitoring samples) should be interpreted as a marker of relapse, especially in dogs following the discontinuation of treatment.

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Management of Leishmania-seropositive but clinically healthy dogs and


PCR-positive but seronegative dogs
Management of dogs with no clinical signs and laboratory abnormalities
Seropositive

SeroNegative

What to do
Monitor every 36 months.
Evaluate seroconversion.
Evaluate possible development
of illness.

Monitoring

Retest to confirm seropositivity.


Monitor with physical examination,
routine laboratory tests, and serological
tests every 36 months.

Treatment not recommended

Prevention
Protect with topical insecticide repellents to minimize the transmission of L. infantum.

It is recommended to use serology alone or the combination


of serology with PCR for screening healthy dogs and to avoid
screening clinically healthy dogs only by PCR.

B 
Confirmed seropositive dogs should be monitored periodically
with physical examinations, routine laboratory, and serological
tests on a regular basis every 36 months to assess the
possible progression of infection towards disease.

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LEISHVET GUIDELINES FOR THE PRACTICAL MANAGEMENT OF CANINE LEISHMANIOSIS (CanL)

PREVENTION
Effective prevention of sand fly bites can be achieved when the following steps are taken: (i) keeping the
dog indoors during the sand fly season from dusk to dawn; (ii) reducing the microhabitats favorable to
sand flies in the vicinity of the house or in locations where the dog spends time; (iii) usage of environmental
insecticide treatment, and (iv) usage of topical insecticides with proven activity against the sand flies which
bite dogs.
In recent years, various insecticide formulations have been evaluated under laboratory and field conditions with encouraging results. Field studies have shown that some topical insecticides used in canine
populations have been effective in reducing the transmission of infection in both dogs and humans.
Veterinarians and dog owners are advised to check the label recommendations of products and follow the
manufacturers instructions, especially for the correct application of the product and frequency of reapplication. Client education on the maintainance of appropriate insecticide throughout the period of sand fly
activity is also crucial for the protection of dogs.
Preventive measures in dogs from non-endemic areas travelling to endemic areas should be the same as
for healthy or sick dogs that live in endemic areas. As recommended for dogs living in the endemic areas,
advice should be given for follow-up visits after returning for clinical and laboratory checkup.
Prevention should be an integrated approach including vaccination against L. infantum with an effective
vaccine and the application of a topically applied insecticide with repellent properties throughout the
period of sand fly activity.
Topical insecticides applied to dogs living in or travelling to endemic areas to be maintained during the
entire period of potential exposure to/or activity of sand flies:

 ermethrin/imidacloprid, as a spot-on formulation. Treatment provides repellent (anti-feeding)


P
activity against sand flies (Phlebotomus perniciosus) for three weeks. It is recommended to repeat
administration every 3 weeks in dogs living outdoors. It should be applied at least 2 days before travelling or before exposure.

Deltamethrin-impregnated collars. Control of feeding by phlebotomine sand flies (P. perniciosus) for
B 
a period of 56 months. Replace collar every 56 months. It should be applied at least 12 weeks
before travelling or before exposure.

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REFERENCES
Baneth G, Koutinas AF, Solano-Gallego L, Bourdeau P, Ferrer L: Canine leishmaniosis new concepts
and insights on an expanding zoonosis: part one. Trends Parasitol 2008; 24:324330
M
 ir G, Cardoso L, Pennisi MG, Oliva G, Baneth G: Canine leishmaniosis new concepts and insights on
an expanding zoonosis: part two. Trends Parasitol 2008; 24(8):371377
S olano-Gallego L, Koutinas AF, Miro G, Cardoso L, Pennisi MG, Ferrer L, Bourdeau P, Oliva G, Baneth G:
Directions for the diagnosis, clinical staging, treatment and prevention of canine leishmaniosis.
Vet Parasitol 2009; 165:118
S olano-Gallego L, Mir G, Koutinas AF, Cardoso L, Pennisi MG, Ferrer L, Bourdeau P, Oliva G, Baneth G:
LeishVet guidelines for the practical management of canine leishmaniosis. Parasites & Vectors 2011; 4:86.
www.esccap.com

Prevention

www.leishvet.org

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LEISHVET GUIDELINES FOR THE PRACTICAL MANAGEMENT OF CANINE LEISHMANIOSIS (CanL)

About LeishVet
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. LeishVets main goal is to improve the knowledge on
different aspects of leishmaniosis in veterinary medicine and public health, including the development of
consensus recommendations based on recent evidence-based literature and clinical experience that would
represent the most current understanding of L. infantum infection in dogs and other animals.

LeishVet Members

G. Baneth | Hebrew University, Rehovot, Israel


P. Bourdeau | Ecole Nationale Vtrinaire, Agroalimentaire et de lAlimentation,
Nantes-Atlantique (ONIRIS), Nantes, France
L. Cardoso | University of Trs-os-Montes e Alto Douro, Vila Real, Portugal
L. Ferrer | Universitat Autnoma de Barcelona, Bellaterra, Cerdanyola del Valls (Barcelona), Spain
A. F. Koutinas | Aristotle University of Thessaloniki, Thessaloniki, Greece
G. Mir | Universidad Complutense de Madrid, Madrid, Spain
G. Oliva | Universita di Napoli, Napoli, Italy
M. G. Pennisi | University of Messina, Messina, Italy
L. Solano-Gallego | Universitat Autnoma de Barcelona, Bellaterra, Cerdanyola del Valls
(Barcelona), Spain

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About LeishVet

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Mailing address:
LeishVet, Veterinary Faculty,
Universidad Complutense de Madrid,
Av. Puerta de Hierro s/n,
28040 Madrid, Spain
E-mail: leishvet@vet.ucm.es
Web page: www.leishvet.org
1st Edition October 2011
Sponsorship:

Bayer Animal Health

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