Leishmaniosis in dogs Simple Steps for In Clinic …...the field of parasite prevention. Canine...
Transcript of Leishmaniosis in dogs Simple Steps for In Clinic …...the field of parasite prevention. Canine...
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Leishmaniosis in dogsSimple Steps for In Clinic Diagnosis
18 March 2020– Dr. Inbal Peled, Biogal
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✓ Leishmaniasis is endemic in 88 countries on five continents—Africa, Asia, Europe, North America and South America.
✓ 12 million people are affected by leishmaniasis✓ 50 000 to 90 000 new cases of VL occur worldwide
annually✓ An estimated 600 000 to 1 million new cases of CL
occur worldwide annually.
HUMAN LEISHMANIASIS
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Human Leishmaniasis - cont
• Mostly affects poor people
• Associated with:
- malnutrition,
- population displacement,
- poor housing,
- weak immune system
- environmental changes:
deforestationbuilding of dams
irrigation schemes urbanization
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Human Leishmaniasis – clinical signs
MucocutaneousCutaneous (most common)
Visceral (most serious form)
partial or total destruction of mucous membranes of the nose, mouth and throat
• irregular bouts of fever• weight loss• Enlarged spleen and liver• Anemia
skin lesions, mainly ulcers, on exposed parts of the body, leaving life-long scars
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Canine LeishmaniosisL. Infantum
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Leishmaniosis in dogs,Simple steps for in clinic Diagnosis
✓ General aspects of the disease
✓Clinical signs
✓Diagnostics options
✓ In-clinic diagnostics
✓ Disease staging and prognosis
Topics
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Leishmania Infantum Canine infection -General aspects
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Canine Leishmaniosis
Cutaneous LeishmaniosisVisceral Leishmaniosis
Leishmania braziliensis*
Leishmania amazonensis
Leishmania infantum
Because the internal
organs and skin of
the dog are affected,
the canine disease
is termed
viscerocutaneous
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WORLD CANINE LEISHMANIA DISTRIBUTION
http://www.cvbd.org/en/occurrence-maps/world-map/
The CVBD World
Forum is supported
by Bayer Animal
Health, a specialist in
the field of parasite
prevention.
Canine leishmaniosis is extremely common in the Mediterranean area and South America; -also found in Africa, Asia, Central America
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Prevalance of L.infantum (2014)
• Spain, France, Italy and Portugal – 2.5 million
• Spreading to North Europe – Alps, Pyrenees, and north western Spain.
• South America – estimation ~ Millions • Highest in Brazil (90% of cases) and Venezuela
• Highly endemic countries• canine infection rates 70-90% • Balearic islands of Spain, Greece, Marseille area France, Naples area in Italy.
Canine leishmaniosis is extremely common in the Mediterranean area and South America;
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Transmission modesSand fly transmission
Sand fly bite Dermis
Macrophages penetration and
replicationBlood
Lymph nodes, Spleen, bone
marrow, whole body
promastigotes
amastigotes
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Non sand fly transmission
✓Blood products from carriers
✓Vertical
✓Venereal
Suspected yet unproven
✓ direct dog-to-dog transmission through bites or wounds
✓ other blood feeding arthropods (ticks and fleas)
Transmission modes - cont
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Canine Leishmaniosis – L. Infantum
Incubation period:
3 months – 7 years
Higher Incidence
• Age at least 2 years
• Prolonged exposure to the outdoors
• Lack of topical insecticide use
• Short haircoat
• Breeds - Rottweilers, GSD and Boxers
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Chronic subclinical infection40-80%
Self limited disease
Fatal disease
L.infantum infection outcome
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The dog as a reservoir of L.Infantum
Long pre-patent period of infection
High concentration of protozoan amastigotes in the skin
Complete eliminationof the parasite is uncertain
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Factors influencing infection outcome
OthersHost relatedParasite related
Stress
Immunosuppressive treatment
Immune status
Genetics
Susceptible breeds
Nutritional state
Co-infections
Other non-infectious debilitating diseases
Strain
VirulenceParasitic load
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Proliferation in macrophages, lymphocytes, plasma cells
Lymphadenomegaly
Splenomegaly
Hyperglobulinemia
Granulomatous lesions in the skin
Over antibody production
Immune-complexes deposits in the
kidneys, joints, eye and blood vessel
walls.
Immune mediated hemolytic anemia
Co -infections
Ehrlichiosis
Hepatozoonosis
L. Infantum Pathogenesis
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Canine Leishmaniosis,L.infantumDiagnosis
•History
•Clinical Findings
• Laboratory Findings
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Main purposes for the diagnosis of L. infantum infection
Disease confirmation
Imported dogs
Blood donors
Breeding dogs (vertical transmission / presence in semen…)
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Clinical diagnosis challenges
• Almost 50% of the affected canine population does not exhibit clinical signs
• When ill – variable clinical signs and nonspecific • Any organ can be involved• Lab findings not disease specific
(thrombocytopenia, anemia, renal disease….)• more diagnostic methods – each one has some
limitations
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Typical clinical findings and history
• Skin lesions (90%)
• Weight loss
• Exercise intolerance
• Decreased appetite
• Lethargy
• Lameness
• Vomiting, and Diarrhea
• Lymphadenomegaly
local or generalized
• Splenomegaly
• Polyuria and polydipsia
• Ocular lesions
• Epistaxis
• Onychogryphosis
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Variable Cutaneous lesions
• Exfoliative dermatitis with/without alopecia
• Nodular, popular or pustular dermatitis
• Erosive ulcerative dermatitis
• Nasal hyperkeratosis
• Onychogryphosis (abnormal nail growth)
Mucocutaneous ulcerationExfoliative dermatitis
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Skin ulceration on the ear Exfoliative dermatitis
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Visceral LeishmaniosisMucocutaneous lesion
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Cutaneous signs - basic facts
• Visceral involvement
• Rarely pruritic
• Generalized or localized
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Occular signs
Uveitis
• Anterior Uveitis
• Keratonconjunctivitis
• Blepharitis
Conjunctivitis and blepharitis
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• Muscular atrophy
• Skin Lesions
• Weight loss
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Canine LeishmaniosisLaboratory Abnormalities
CBC
• Anemia (mild to moderate non regenerative)
• Thrombocytopenia
Serum Biochemistry
• Hyperproteinemia
• Hyperglobulinemia
• Hypoalbuminemia
• Renal azotemia
• Elevated liver enzymes
Urinalysis
• Proteinuria
• Isosthenuria (depending on renal
stage)
Laboratory Abnormalities
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Canine Leishmaniosis – Specific Diagnostic methods
• Parasitological: cytology/histology(requires experience in slide examination)
✓ Skin lesions✓ Bone marrow ✓ Spleen ✓ Lymph Node✓ Liver ✓ Rare- WBC
• Serological
• Molecular: PCR
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• IFAT: Indirect Fluorescent Antibody Test• Cross reactivity with other Trypanosoma spp
• ELISA• Higher specificity • Technically easier to perform
• Rapid lateral flow
.Qualitative
.Quick, simple, yes/no result
.point of care test
Serology
Canine Leishmaniosis diagnostics
• Negative serologic test results may reflect delayed seroconversion in some animals, which can take several months to occur
• Affected by vaccination• Performed in a referral Lab
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SEROLOGIC TESTSLimitations
✓Goal: Detection of Antibodies in the blood
✓Antibodies indicate exposure to pathogen (past and present) but not necessarily disease
✓Antibodies develop within 3 weeks after infection (following establishment of disease)
✓Antibodies can persist for months to years post exposure without presence of disease
✓Antibodies can persist regardless of effective treatment
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MOLECULAR TESTSPolymerase Chain Reaction (PCR)
✓ Traditionally restricted to high complexity laboratories with dedicated space and equipment.
✓ New technology is now available for use in regular clinical laboratory environments.
✓ Detects and amplifies a specific sequence of of the
pathogen’s DNA
✓ Allows for sensitive and specific diagnosis of infection
✓ Monitoring treatment efficacy
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Biogal’s PCRundiagnostic devices
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Molecular detection- PCR
✓First choice samples: bone marrow, lymph node, skin and conjunctival swabs.
✓ Less sensitive samples: blood, buffy coat and urine.
✓Most sensitive technique: real-time PCR.
✓Results are not affected by vaccinations (DNA not present in the vaccine)
✓ PCRun: in-clinic diagnosis
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Source: LeishVet guidelines for the practical management of canine leishmaniosis
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Clinical stages Serology PCR Clinical signs Laboratory findings Prognosis
Stage I Mild disease
Negative to low positive antibody
levels+
mild clinical Lymphadenomegaly/papular
dermatitis
Usually normalcreatinine < 1.4 mg/dl;
non-proteinuric: UPC < 0.5Good
Stage II Moderate
disease
Low to high positive antibody
levels+
stage I + Cutaneous lesions
anorexia, weight loss,
fever, epistaxis
• Mild non-regenerative anemia
• High Glob
• Low Alb
• serum hyperviscositysyndrome
Normal renal profileUPC < 0.5
Good to guardedCreatinine <1.4 mg/dl;
UPC = 0.5-1
Stage III Severe disease
Medium to high positive antibody
levels+
stages I and II, +immune-complex related
lesions: vasculitis, arthritis, uveitis
glomerulonephritis.
Creatinine < 1.4 mg/dl; UPC > 1 Guarded
to poorCKD stage II(Creatinine 1.4 -2 mg/dl)
Stage IV Very severe
disease
Medium to high positive antibody
levels+
stage III + Pulmonary thromboembolism,
nephrotic syndrome end stage renal disease
CKD stage III (creatinine 2-5 mg/dl)
PoorCKD stage IV (creatinine > 5
mg/dl)
Nephrotic syndrome: marked proteinuria UPC > 5
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Leishmania infantum canine infection
Meglumine Antimoniate, Allopurinol, Miltefosine, Domperidone
Prevention:
• Vector control- Parasiticides with repellent activity
• Vaccines
Prognosis: Good to poor depending on disease stage
• Treatment is rarely, if ever, curative and dogs usually remain infected for life
• With no treatment - death within 2-3 years from onset of clinical signs due to renal failure.
Treatment
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PARAMETERS
➢ Clinical history and physical examination
➢ CBC, Biochemistry
➢ Complete urinalyisis & UPC
➢ Quantitative serology*
➢ PCR
FREQUENCY
Sick treated dogsClinically healthy
Infected dogs
After the first month of treatment and then every 3-4 months during the first year.
Later on, every 6-12 month in dogs fully recovered clinically with treatment.
Every 3-6 months
Not before 6 months after initial treatment and every 6-12 months
Every 3-6 months
At the same time as serology Every 3-6 months
*Some dogs have a significant decrease in antibody levels (i.e. more than three two-fold dilution difference between monitoring samples) associated with clinical improvement within 6-12 months of therapy. A marked increase in antibody levels (i.e. more than three two-fold dilution difference between monitoring samples) should be interpreted as a marker of disease relapse, especially in dogs following the discontinuation of treatment.
Source: LeishVet guidelines for the practical management of canine leishmaniosis
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Take home messages
• Serology alone DOES NOT provide a definitive diagnosis
• Full comprehensive diagnosis and monitoring:
✓ Physical examination
✓ CBC, Biochemistry, UA
✓ Serology & PCR
• First choice samples for PCR
• Bone marrow / Lymph nodes
• Skin
• Conjunctival swabs
• Buffy coat
• Peripheral blood