leishmania infatum

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Canine leisHManiOsis (C l)LEISHVET BRIEF INFORMATION FOR

THE PRACTICING VETERINARIAN


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COntent

DIAGNOSIS 3

CLINICAL STAGING 6

THERAPY 9

MONITORING 10

PREVENTION 12

REFERENCES 13

ABOUT LEISHVET 14

LEISHVET MEMBERS 14

LEISHVET GUIDELINES FOR THE PRACTICAL MANAGEMENT OFCANINE LEISHMANIOSIS (CanL)


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diagnOsis

Diagnosis is performed based on physical and clinicopathological manifestations andby conrmation of infection, using mainly serological and molecular techniques.

Main purposes for the diagnosis of Leishmania infantum infection:

A Conrm presence of the disease.

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

C Screen blood donors.

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diagnOstiC apprOaCH

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

NEGATIVE

NEGATIVE Considerother

diagnoses

ConrmedCanL

Highsuspicionof CanL

Cytological/histologicalevaluation

Quantitative serology

Leishmania amastigotes

POSITIVE

POSITIVE

LOW

NO

PCR

YES

HIGH

D I A G N O S I S


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CliniCal ManifestatiOns labOratOry abnOrMalities

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

Serum proteins and electrophoretogram Hyperglobulinemia

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

Cutaneous Non-pruritic exfoliative dermatitis

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

CBC/Hemostasis Mild to moderate non-regenerative

anemia Leukocytosis or leukopenia Thrombocytopathy Thrombocytopenia Impaired secondary hemostasis and

brinolysis

Ocular Blepharitis (exfoliative, ulcerative,

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

Biochemical prole/urinalysis Mild to severe proteinuria Renal azotemia Elevated liver enzyme activities

Other Mucocutaneous 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

Clinical manifestations and laboratory abnormalities found

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Sand y (Phlebotomus spp.)feeding on a human nger( Photo by R. Pospischil, Monheim,Germany)


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n CanL due to infection with L. infantum

infeCted but HealtHy versus siCk dOgs

A Dogs with clinical leishmaniosis are those presenting suggestive clinical signs and/or clinicopatho-logical abnormalities, and having a conrmed L. infantum infection.

B Dogs with subclinical infection (or clinically healthy but infected dogs) are those that present neitherclinical signs on physical examination nor clinicopathological abnormalities on routine laboratory tests(CBC, biochemical prole and urinalysis) but have a conrmed L. infantum infection.

diagnOstiC MetHOds A Parasitological: cytology/histology, immunohistochemistry and culture.B Molecular: conventional, nested and real-time polymerase chain reaction (PCR).C Serological: quantitative (IFAT and ELISA) and qualitative (rapid tests).

saMples and teCHniques tO be used fOr pCr A Samples recommended (more sensitive tissues):

bone marrow lymph node

spleen skin

conjunctiva

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

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Intracellular Leishmaniainfantum amastigoteswithin a dogs macrophage(bone marrow cytology;Giemsa-stained bloodsmear) ( A. F. Koutinas, Thessaloniki, Greece)

D I A G N O S I S


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CliniCal stages serOlOgy* CliniCal signs

Stage I

Mild disease

Negative to low positiveantibody levels

Mild peripheral lymphadenomegaly papular dermatitis

Stage II

Moderate disease

Low to high positiveantibody levels

Stage I signs plus: diffuse or symmetricalcutaneous lesions such as exfoliative derma-titis/onychogryphosis, ulcerations (planumnasale, footpads, bony prominences, muco-cutaneous junctions), anorexia, weight loss,fever, and epistaxis

Stage III

Severe disease

Medium to high positiveantibody levels

Dogs which apart from the signs listed instages I and II may present signs originatingfrom immune-complex lesions: vasculitis,arthritis, uveitis, and glomerulonephritis

Stage IV

Very severe disease

Medium to high positiveantibody levels

Dogs with clinical signs listed in stage III:pulmonary thromboembolism, or nephroticsyndrome and end-stage renal disease

CliniCal staging

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

Clinical staging of CanL based on serological status, clinical signs,laboratory ndings, and type of therapy and prognosis for each stage

* Dogs with negative to medium positive antibody levels should be conrmed as infected by other diagnostic techniques such ascytology, histology, immunohistochemistry, or PCR. High levels of antibodies dened as a three- to fourfold elevation above thecut off level of a well-established refer ence laboratory are conclusive of a diagnosis of CanL.

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labOratOry findings tHerapy prOgnOsis

Usually no clinicopathological abnormalities observed

Normal renal prole: creatinine < 1.4 mg/dl; non-protein uric: UPC < 0.5

Treat with anti- Leish- mania short-termtherapy or monitorwithout treatment**

Good

Clinicopathological abnormalities such as mildnon-regenerative anemia, hyperglobulinemia,hypo albuminemia, serum hyperviscosity syndrome

Substage a) Normal renal prole: creatinine < 1.4 mg/dl;

non-proteinuric: UPC < 0.5

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

Allopurinol + meglumineantimoniate orallopurinol + miltefosine

Good to guarded

Clinicopathological abnormalities listed in stage II:

Chronic kidney disease (CKD) IRIS stage I with UPC > 1or stage II (creatinine 1.4 2 mg/dl)

Allopurinol + meglumineantimoniate orallopurinol + miltefosine

Follow IRIS1 guidelines for CKD

Guarded to poor

Clinicopathological abnormalities listed in stage II:

CKD IRIS stage III (creatinine 2 5 mg/dl) andstage IV (creatinine > 5 mg/dl)

Nephrotic syndrome: marked proteinuria UPC > 5

Allopurinol (alone)

Follow IRISguidelines for CKD

Poor

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 prolongedtreatment with one or two combined drugs or alternatively monitoring with no treatment. However, there is limited informationon dogs in this stage and, therefore, treatment options remain to be dened.

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Sand y(Phlebotomus spp.)

C L I N I C A L S T A G I N G


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som c c o C l

A EpistaxisB Bilateral uveitis and corneal opacityC Purulent conjunctivitis and blepharitisD Exfoliative alopecia in the rear leg and popliteal lymphadenomegalyE Marked cachexia and generalized exfoliative alopecia


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tHerapyCurrent treatment protocols for CanL

drugs dOsages Main side effeCtsMeglumine antimoniate* 75 100 mg/kg once a day or

40 75 mg/kg twice a day for4 weeks S.C.**

Potential nephrotoxicity Cutaneous abscesses/

cellulitis

Miltefosine* 2 mg/kg once a day for 28 daysP. O.

Vomiting Diarrhea

Allopurinol 10 mg/kg twice a day for at least6 12 months P. O.

Xanthine urolithiasis

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 by2 3 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 scientic experience by theLeishVet members. These recommendations have been published in scientic peer-reviewed journals. Veterinary practitionersare requested to check with product leaets and product registrations in their related country prior to any product selection and

initiation of treatment.

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T H E R A P Y


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MOnitOringRecommended monitoring of clinicopathological parameters and serologyduring and after treatment of CanL

paraMeter frequenCy

Clinical and laboratory: Anamnesis (clinical history) Complete physical examination CBC

Biochemical proles Serum electrophoresis (optional) Urinalysis (incl. UPC in case of a

proteinuric patient)

After the 1 st month of treatment Every 3 4 months during the 1 st 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 scientic status: not recommended unlesscombined with serology

* Possible serological ndings following therapy:Some dogs present a signicant decrease in antibody levels (more than a twofold dilutions difference between the rst and thefollowing samples) associated with clinical improvement within 6 months to 1 year of treatment. Other dogs might not have adecrease in antibody levels despite clinical improvement. In contrast, a marked increase of antibody levels (more than two-foldelevation between monitoring samples) should be interpreted as a marker of relapse, especially in dogs following the dis continu-ation of treatment.


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Management of Leishmania -seropositive but clinically healthy dogs andPCR-positive but seronegative dogs

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

Management of dogs with no clinical signs and laboratory abnormalities

SEROPOSITIVE SERONEGATIVE

What to do

Retest to conrm seropositivity.Monitor with physical examination,routine laboratory tests, and serologicaltests every 3 6 months.

Monitor every 3 6 months. Evaluate seroconversion. Evaluate possible development

of illness.

A It is recommended to use serology alone or the combinationof serology with PCR for screening healthy dogs and to avoidscreening clinically healthy dogs only by PCR.

B Conrmed seropositive dogs should be monitored periodicallywith physical examinations, routine laboratory, and serologicaltests on a regular basis every 3 6 months to assess thepossible progression of infection towards disease.

Prevention

Treatment not recommended

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M O N I T O R I N G


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preventiOn

Effective prevention of sand y bites can be achieved when the following steps are taken: (i) keeping thedog indoors during the sand y season from dusk to dawn; (ii) reducing the microhabitats favorable tosand ies in the vicinity of the house or in locations where the dog spends time; (iii) usage of environmentalinsecticide treatment, and (iv) usage of topical insecticides with proven activity against the sand ies whichbite dogs.

In recent years, various insecticide formulations have been evaluated under laboratory and eld condi-tions with encouraging results. Field studies have shown that some topical insecticides used in caninepopulations 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 themanufacturers instructions, especially for the correct application of the product and frequency of reappli-cation. Client education on the maintainance of appropriate insecticide throughout the period of sand yactivity is also crucial for the protection of dogs.

Preventive measures in dogs from non-endemic areas travelling to endemic areas should be the same asfor 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 theperiod of sand y activity.

Topical insecticides applied to dogs living in or travelling to endemic areas to be maintained during theentire period of potential exposure to/or activity of sand ies:

A Permethrin/imidacloprid, as a spot-on formulation. Treatment provides repellent (anti-feeding)activity against sand ies ( Phlebotomus perniciosus ) for three weeks. It is recommended to repeatadministra tion every 3 weeks in dogs living outdoors. It should be applied at least 2 days before travel-ling or before exposure.

B Deltamethrin-impregnated collars. Control of feeding by phlebotomine sand ies ( P. perniciosus) fora period of 5 6 months. Replace collar every 5 6 months. It should be applied at least 1 2 weeksbefore 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; 24:324 330

Mir G, Cardoso L, Pennisi MG, Oliva G, Baneth G: Canine leishmaniosis new concepts and insights onan expanding zoonosis: part two. Trends Parasitol 2008; 24(8):371 377

Solano-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

Solano-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 leish maniosis. Parasites & Vectors 2011; 4:86. www.esccap.com

www.leishvet.org

P R E V E N T I O N


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leisHvet MeMbers

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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


abOut leisHvetLeishVet is a group of veterinary scientists from academic institutes in Europe and the Mediterranean basinwith a main clinical and scientic interest in CanL. LeishVets main goal is to improve the knowledge ondifferent aspects of leishmaniosis in veterinary medicine and public health, including the development ofconsensus recommendations based on recent evidence-based literature and clinical experience that wouldrepresent the most current understanding of L. infantum infection in dogs and other animals.


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B O U T L E I S H V E T


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Sponsorship:

Bayer Animal Health

Mailing address:LeishVet, Veterinary Faculty,Universidad Complutense de Madrid,Av. Puerta de Hierro s/n,28040 Madrid, Spain

E-mail: [email protected] page: www.leishvet.org

1st Edition October 2011

leishmania infatum

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