Shared Flashcard Set

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Leishmania
Vet dermatology
26
Veterinary Medicine
Professional
10/13/2021

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Cards

Term
Leishmaniasis sensitive individuals (why infection occurs in certain dogs)
Definition

-Type 2 response not protective- promotes antibody production

-Cytokines inhibitory to cell killing mechanisms

-Fungal disease and leishmania protection requires an effective type 1 response (need cells to produce IFN-gamma and TNF-alpha) then macrophages can move in to bash organism and clear infection!

Term
Leishmania infantum cause
Definition

-Protozoa, Trypanosomidae

-Biphasic parasite: needs 2 different hosts

-Promastigote (Flagellate), 15um long, found in vector and cultures

-Amastigote (without flagellum), 2-5um long, in vertebrate hosts, often in macrophages (within the cell)

-transmitted by sand flies (Plebotomus spp., 2-3mm, small, nocturnal, limited roaming, rural areas)

-Mediterrean region

Term
Epidemiology of Leishmania in dogs
Definition

-M>F; 2-4 years and > 7 years of age

-rarely seen in very young dogs

-long incubation time (4 months to 7 years)

-some breeds are resistant (Ibizan hound)

-GSD, Rotties, Boxers are more affected

-Immunosuppressed animals are predisposed

-seen in endemic area, 10-40% of dogs are seropositive

-30-60% of seropositive dogs are asymptomatic

-80% will develop disease

Term
Development of disease in a Leishmania dog (what makes a resistant vs. sensitive dog?)
Definition

Resistant dog: temporary seropositive, no clinical signs, strong Th1 (cellular immunity), high IFNgamma, TNF, IL2, and IL12

Sensitive dog: high serum titres, clinical disease, weak Th1/high Th2 (humoral immunity), cytokines are produced IL4, IL5, IL6 and IL10

Term
Why is humoral immunity detrimental in Leishmania?
Definition

-antibodies are not protective

-formation of immune complexes which deposit in basal membranes of joints, kidneys, blood vessels, and eyes (vasculitis, glomerulonephritis, polyarthritis, and uveitis)

-opsonization of parasites may increase phagocytosis and result in infection

-impairment of cell mediated immune system

Term
Systemic signs of Leishmania dog
Definition

-Weakness and decreased activity

-locomotory problems, lameness

-liver, pancreas, intestinal disease

-renal insufficiency, failure

-less frequent heart disease and thrombosis

-epistaxis

-lymphadenopathy

-ocular lesions

Term
Cutaneous lesions of Leishmania
Definition

-symmetrical alopecia and dry exfoliation (most frequent form in 60% of animals)

-starts on head and spreads to body

-ulcerative form (23% of cases) may affect bony prominences, mucocutaneous junctions and extremities (probably due to vasculitis)

-multiple nodules of variable sizes may develop around skin, eyelids and mucosae (~12% animals). Young resistant dogs are probably inoculation site

-may also develop nasal/digital hyperkeratosis, onychogryphosis, paronychia, nasal/oral depigmentation, ulcerative stomatitis, mucosal proliferations on penis, tongue, nose and mouth

Term
Name the clinicopathological findings seen in Leishmania
Definition

-high serum proteins (usually over 8 gr/dl) unless severe loss with urine

-hyperglobulinaemia (polyclonal B-cell activation and Ig production)

-Hypoalbuminaemia (compensatory or due to protein-losing nephropathy, hepatopathy)

-Typically, "Two horns" are seen on protein electrophoresis (low albumin/globulin ratio of <1)

-CBC/kidney evaluation reveals mild, non-regenerative anaemia, thrombocytopenia and coagulation disorders

-Increased urea, later increased creatinine

-Protein/creatinine ratio in urine >0.5

-Acute-phase proteins (APP) include C-reactive protein, haptoglobin, amyloid A (may be useful in monitoring of therapy, these APPs are all increased in animals with active disease)

Term
Leishmania cytological diagnosis. Name the best places to sample to find organism
Definition

-100% specificity, low specificity

-Lymph nodes (30%)- afferent lymph nodes from skin lesions more positive

-Bone marrow (50-70%)- best to sample costo-chondral jxn, iliac crest, and sternum. Leishmania found in macrophages

-Spleen is most rewarding

-Sample cytology under crusts and scales

-FNAB cytology from skin nodules and plaques

Term
Diagnosis of Leishmania via histopathology
Definition

-Dermatopathology H and E, Giemsa (good from scaly skin and papules), scarce in ulcerative form

-Immunohistochemistry

Term
Measurement of circulating Ab via serology in Leishmania
Definition

-IFAT, Dot-ELISA, direct agglutination

-high sensitivity and specificity (80-100%)

-in house snap tests are less reliable, OK for screening

-false positive: recent contact in the resistant dog (test in Winter--- March/April)

-false negative: prepatent phase in affected dogs (retest after 6-8 weeks)

-serology is NOT suitable for monitoring of treatment, as they remain measurable after remission

Term
Diagnosing Leishmania via molecular methods (e.g.PCR). Is it a good or bad test?
Definition

-Real time PCR of kinetoplastic DNA is highly specific and sensitive

-Requires fresh and formalin fixed tissue

-FNAB of lymph node, bone marrow and SPLEEN

-CONJUNCTIVAL SWABS detection of early positivity

-may recognize leishmanial DNA in animals which have been clinically cured for years (false positive?) and in healthy carriers

-Quantitative PCR for monitoring therapy

Term
When should I treat a Leishmania dog?
Definition

-Healthy- infected resistant

-Serology negative with positive PCR

-Serology low to medium

-No treatment

-Monitor serology every 3-6 months (by 2-fold increase start treatment)

-Treat clinically ill with serology high and PCR positive

-Treatment following staging

-Guidelines via LeishVet Group

-Need to perform clinical staging of leishmaniosis (4 stages)

-laboratory tests to be done (CBC/general panel including renal values, blood protein electrophoresis and TP; urine analysis with sediment and P/C)

Term
Therapeutic options for Leishmania in dogs
Definition

-No treatment

-Allopurinol alone (inhibits xanthine oxidase)

-Antimonials alone (pentavalent antimonials bind to polypeptides, inhibit DNA topoisomerase glycolytic enzymes and fatty acid beta oxidation)

-Miltefosine alone (exerts activity by inhibiting cytochrome c oxidase and causing apoptosis-like cell death. This may affect membrane integrity and mitochondrial function of the parasite)

-Miltefosine + allopurinol

-Antimonials +allopurinol

Term
Glucantime (N-metil D-glucamine) common drug name and what is it used to treat?
Definition

-Meglumine antimoniate

-used to treat leishmaniasis (classical therapy)

-given by injection into a muscle

-side effects include loss of appetite, nausea, abdominal pain, cough, feeling tired, muscle pain, irregular heartbeat, and kidney problems

-belongs to a group of medications known as the pentavalent antimonials

-Pentavalent antimonials bind to polypeptides, inhibit DNA topoisomerase glycolytic enzymes and fatty acid beta-oxidation. Electron microscopy studies show antimonial-induced changes in parasite cell membranes.

Term
Domperidone MOA and use in Leishmania
Definition

-a dopamine D2 receptor antagonist which stimulates the release of serotonin----> production of prolactin occurs---> stimulation of cell-mediated immunity

-Leishguard (Esteve) and on the market in Spain and Italy

-Used as an immunostimulator

-Both in prevention in healthy dogs and as therapy in diseased animals

-Inexpensive and safe!

Term
Monitoring of therapy in Leishmania
Definition

-Protein electrophoresis on day 30, 90 and every 6 months thereafter

-Any other abnormal value (e.g. kidneys)

-Serum testing every 6-12 months (decreases very slowly). For negative serum titre (good immunological recovery and need to perform PCR for parasitological cure)

-For a 2 fold increase (evidence of relapse)

-RT-PCR used when patient is serology negative

-Acute phase protein monitoring (high in Leishmania infected)---- C-reactive protein, haptoglobin and amyloid A

Term
Prognosis for Leishmania
Definition

-75% of dogs survive at least 4 years if they are followed with current protocols (including a new treatment course at every relapse)

-Long term remission with long term allopurinol administration

-Worst prognosis if severe renal damage

Term
Prevention of Leishmania
Definition

-Dogs in endemic areas should not spend the night outside

-Fine mesh net should be applied to windows

-Repellents on animals in the environment (DEET, piperonylbutoxide)

-Pyrethroid collars (e.g. Scalibor, Seresto/Foresto), permethrin spot-on have repellent activity when given every 3-4 weeks

Helpful Reminder:

-MOA of Pyrethroids (axonic excitotoxins)- toxic effects are mediated through preventing the closure of voltage-gated sodium channels in axonal membranes

-MOA of Permethrin is to act on the nerve cell membrane to disrupt the sodium channel current

Term
Leishmania Vaccine information
Definition

-Canileish brand

-excreted secreted proteins, parasite surface antigen and saponin: stimulates the cell-mediated immune system and production of IFN-gamma

-Only in seronegative dogs

-3 injections the first year then annual thereafter

-It causes seroconversion (positive IFI)

-In order to differentiate vaccinated from diseased animals, a special test is needed

Term
Best place to perform cytology for Leishmania
Definition
  • Spleen is the most rewarding
  • Lymph nodes (30%)- afferent lnn from skin lesions more positive
  • Bone marrow (50-70%)- Leishmania found in macrophages
  • Sample under crusts and scales
  • FNAB cytology from skin nodules/plaques
Term
Common Clinicopathological findings in Leishmania
Definition
  • High serum proteins (usually over 8 gr/dl) unless severe loss in urine
  • hyperglobulinemia (polyclonal B cell activation and Ig production)
  • hypoalbuminemia (compensatory or due to protein losing nephropathy, hepatopathy)
  • typical "two horns" protein electrophoresis
    • low albumin/globulin ratio (<1)
Term
Diagnosis of Leishmania via serology
Definition
  • Measurement of circulating antibody via IFAT, Dot-ELISA, direct agglutination
  • high sensitivity and specificity (80-100%)
  • in house snap tests are less reliable (ok to screen)
  • False positives due to recent contact with resistant dog (test in winter March/April)
  • False negatives due to prepatent phase in affected dogs (retest after 6-8 weeks)
  • not suitable for monitoring of treatment-remain measurable after remission
Term
Molecular diagnosis via PCR
Definition
  • highly specific and sensitive
  • use fresh and formalin fixed tissue
  • FNAB of lymph node, bone marrow and spleen
  • Conjunctival swab for detection of early positive
  • may recognize leishmanial DNA in animals which have been clinically cured (false positive?) and in healthy carriers
  • PCR for monitoring therapy
Term
When to treat Leishmania patient?
Definition
  • Healthy infected and sensitive
    • serology high and PCR positive
    • will develop the disease
  • Clinically ill
    • serology high and PCR positive
Term
Canileish vaccine components
Definition
  • Excreted secreted proteins, parasite surface antigen and saponin: stimulate the cell mediated immune system and produce IFNγ
  • Only use in seronegative dogs
  • 3 injections in the first year then yearly thereafter
  • Causes seroconversion
  • In order to differentiate vaccinated from diseased- need a special test
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