Prion/Protozoa/Parasitic Infections Flashcards
What is Toxoplasma gondii?
Obligate intracellular protozoal parasite
Cats get it from eating rodent containing encysted bradyzoites –>
Cats are definitive host and excrete infectious oocytes in their feces
- T. gondii can sexually reproduce in their intestines
- because cats don’t have Δ-6-desaturase in their intestine = a lot of linoleic acid
- all other hosts are intermediate hosts
Oocysts can survive and remain infective for many months in cold/dry climates
What happens in the immune response to T. gondii?
stimulates production of IL-2 and IFN-γ by the innate immune system –>
elicit a CD4+ and CD8+ T-cell and NK cells
IFN-y also activates of IDO and TDO (responsible for degrading tryptophan)
- starves the parasite
- can result in depletion of tryptophan in the brain of the host
What are the clinical signs associated with a T. gondii infection?
Can be seen in cats that are immunosuppressed or intermediate hosts
- including marine mammals, penguins, and birds
Non-specific signs of sickness, can affect any body organ
- tissue cysts (can be maintained for life of animal)
- liver, brain, GI, kidneys, lymph nodes, hearts, etc
Skin can have pyogranulomatous dermatitis +/- necrotizing vasculitis
- with intrahistiocytic toxoplasma organisms
How do you diagnose T. gondii infections?
FNA of cutaneous cysts (or other organs) to show them in macs
PCR
paired serum samples showing 4-fold rise in titer over 2-3 weeks
What is the typical treatment for T. gondii infections?
clindamycin (good CNS penetration)
What is canine Caryosporosis?
intracellular protozoan parasite in
- snakes and raptors (primary hosts)
- rodents (secondary host)
rare in dogs but can make pustules, plaques, nodules, panniculitis
How do you diagnose canine Caryosporosis infections?
Histopath: pyogranulomatous dermatitis/panniculitis and intralesional organisms
PCR and DNA sequencing
What is the treatment of canine Caryosporosis infections?
TMS, pyrimethamine and high-dose clindamycin (20 mg/kg twice daily)
- dog as able to get clinda monotherapy but relapsed when stopped
What is Neospora caninum?
a coccidian protozoa (obligate intracellular parasite)
Oocysts passed in the feces of the definitive host (canids) –>
- can shed for months
ingested by an intermediate host (ex. cattle, goats, sheep, horses)
can also have transplacental transmission
What is the lifecycle of Neospora and Toxoplasma?
intermediate host ingest oocyst –>
release rapidly dividing tachyzoites –>
disseminate through host –>
differentiate into bradyzoites –>
form cysts in muscle and tissue
What are the clinical signs associated with a Neospora caninum infection?
Neuromuscular degeneration
Abortion esp in cattle and dogs
- Aborted tissues contain large amounts of tachyzoites and bradyzoites
Many clinical signs depending on where cysts are
- cysts in skin can be draining nodules, ulcerative dermatitis
Clinical signs tend to be worse in younger dogs/those affected in utero
How do you diagnose Neospora caninum infections?
Histopathology: nodular pyogranulomatous dermatitis
- tachyzoites in keratinocytes, macs, neuts, endothelial cells
- eosinophilic necrotizing dermatitis with infarcts
PCR, IHC or serology
What is the treatment for Neospora caninum infections?
Clindamycin
(or TMS)
Which breed of dog may be predisposed to atypical cutaneous protozal infections (canine Caryosporosis and Sarcocystis)?
Rottweilers
(personal observation, the case reports both in Rottweiler puppies)
What can Sarcocystis cause in dogs?
multiple cutaneous abscesses with intralesional protozoa
(dog died, treatment was not attempted)
What can Sarcocystis cruzi cause in cattle?
loss of tail switch (“rat tail”)
may develop alopecia of pinnae, neck, rump, and distal limbs
fever, anorexia, hypersalivation, lameness, anemia, and abortion
What can Sarcocystis capricanis cause in goats?
poor hair coat and patchy alopecia
What is babesiosis?
caused by a hemoprotozoan parasites of genus Babesia
- Babesia canis (more common in greyhounds and Gulf Coast)
- Babesia gibsoni (more common in pitties)
How is canine babesiosis spread?
Bite of infested ticks (multiple species)
Spread of infected blood or saliva
- dog fighting
What are the clinical signs associated with canine babesiosis?
waxing/waning fever, lethargy, reduced appetite, anemia, hematuria, etc
oral/cutaneous petechiae/ecchymoses due to leukocytoclastic vasculitis
can also cause alopecia, scale, pad hyperkeratosis, pododermatitis, onychodystrophy
CAN LOOK LIKE SLE (should have negative/low ANA)
How do you diagnose canine babesiosis?
Serum titers
- B. canis: 1:80 or higher
- B. gibsoni: 1:320 or higher
How do you treat canine babesiosis?
doxycycline (though you may not eliminate parasite)
sometimes clindamycin or azithromycin
What is trypanosomiasis?
More common in horses in Africa, Asia, and Central/South America
Trypanosoma trypanosomes are found principally in the blood and tissue fluids
- a few invade tissue cells
- have a terminal kinetoplast, flagellum and tapered ends
transmitted by blood-sucking arthropods and insects
can cause dependent edema, urticarial plaques, and ulcers
- “silver dollar spots”
regional variant names are Nagana, Surra, and Dourine
- Dourine is transmitted via coitus
- Nagana is through tsete flies (glossina) like African Sleeping Sickness
REPORTABLE
What is the treatment for equine trypanosomiasis?
diminazene, suramin, quinapyramine
but many horses remain inapparent carriers
What is besnoitiosis (globidiosis)?
rare disease of horses and goats in Africa and South and Central America
caused by Besnoitia bennetti (probably through eating oocysts) or vectors
nodular disease with parasitic cysts
- with scleral “pearls” (can be elsewhere inside body)
- nodular dermatitis
may be febrile, depressed, weak, and show signs of upper respiratory disease
What are Giardiasis spp. associated with in Cockatiels and Lovebirds and how is it treated?
feather plucking over the torso and self-inflicted trauma to the wing webs
metronidazole, orally twice daily, for 7–10 days
- +/- Vitamin E since it can do the same thing
What can lice/keds transmit in raptors?
haemoprotozoan parasites such as Haemoproteus sp.
- can lead to hemolytic anemia
What are the clinical signs of protozoal infections in fish?
General lethargy, anorexia and death
- Tetrahymena corlissi = ‘guppy killer’
- Pleistophora hyphessobryconis = ‘neon tetra disease’ (infects muscle)
Excess mucus (‘slime disease’) = dull color and grey-blue sheen to skin
White spots on skin (up to 1 mm)
- Ichthyophthirius multifiliis = “Ich/white spot” in freshwater fish
Chichilids can have “hole in head” disease due to Spironucleus spp.
What is scrapie?
a fatal, degenerative disease affecting the nervous systems of sheep and goats
- not transmissable to himans
one of several transmissible spongiform encephalopathies cause by prions
affected animals will compulsively scrape skin against rocks, trees or fences
- seems to be severe pruritus, is bilateral, esp tail head
other signs include excessive lip smacking, ataxia, tremors, and collapse
What are the clinical signs of bovine spongiform encephalopathy (“mad cow
disease”)?
licking, wrinkling nose, head rubbing, and neurological disorders
What is the vector of leishmaniasis?
female sandflies
- Phlebotomus in the Old World (Europe, Africa, and Asia)
- Lutzomyia in the New World (American continent)
are more common in warmer seasons
are active from dusk to early night then again at dawn
What are the three main clinical presentations of leishmaniasis?
infected macrophages can be found in parasitized tissues
- cause granulomatous inflammatory reactions that lead to most symptomatology
1) cutaneous leishmaniasis
- considered most common in humans and dogs
- good for being infectious
2) mucocutaneous/mucosal leishmaniasis
3) visceral leishmaniasis
- L. infantum most frequently causes this
Can also be the designation form 1988:
1) asymptomatic dogs
- some cannot be detected by conventional serological tests
- shown to be highly competent to transmit the parasite to the vector
2) oligosymptomatic dogs (maximum of three clinical signs)
3) symptomatic dogs (severe signs of the disease)
What is the most common species of Leishmania in dogs?
L. infantum/L. chagasi
- L. chagasi more common in Americas, now thought to be the same
there are at least 53 species with at least 20 species causing disease
What can Leishmania spp cross react with on IFA or ELISA?
Trypanosoma cruzi (anywhere from 18-50%)
Where is L. infantum endemic?
Mediterranean basin, southern America, and Central and Southwest Asia
What is the infective stage of Leishmania?
promastigotes
What is the main reservoir host of Leishmania infantum?
dog are considered the main reservoir hosts in urban areas
cats, rabbits/hares, wild rodents, other canids can be hosts as well
- may be some regional variation in primary reservoir hosts
What is the lifecycle of Leishmania?
In mammal:
- sandflies inject meta cyclic promastigotes during blood meals –>
- phagocytized by macrophages –>
- become amastigotes which multiply –>
- break out of macrophages and infect other monocytic cells –>
In sandfly:
- cells with amastigotes transferred during feeding –>
- amastigotes released in the midgut
- transform into procyclic promastigotes (flagellated) –>
- procyclic promastigotes become metacyclic promastigotes –>
- migrate to the pharyngeal valve
How is Leishmania able to live inside macrophages?
remodeling of the parasitophorous vacuole
- hinders the macrophage signaling pathways
What is the immune system response to Leishmania in humans and dogs?
may not progress to a noticeable form of the disease
- 10-50% of seropositive dogs have no clinical signs
persistent disease is associated with a mixed Th1/Th2 response
related to nutritional/immune state of dogs, dog age/breed, and parasite strain
Th1 cytokines (IFN-γ, TNF-α, and IL-2)
- activate macrophage (M1) to eliminate it with nitric oxide and other ROS
- CD8+ cells can kill affected macrophages and help with more Th1
- CD4+ T can also lyse infected macrophages
- results in productive antibodies (ex. IgG2b,c)
- provides lifelong immunity to reinfection
Th2 cytokines (IL-10, IL-13, IL-4, and TGF-β)
- lead to a humoral response and M2 macrophages so it can survive
- results in non-productive antibodies (ex. IgG1)
Which TLR is significantly upregulated in damaged skin of sick dogs with Leishmania and is associated with disease progression?
TLR2
Which TLR is down regulated in the unaffected skin in infected dogs when
compared with skin from more severely affected dogs?
TLR7
What are the clinical signs of Leishmaniasis?
infected macrophages can be found in parasitized tissues, causing granulomatous inflammatory reactions that lead to most symptomatology
What is the main cause of death in canine leishmaniasis?
Renal failure (glomerulonephritis due to immune-complex deposition)
- proteinuria and high blood creatinine levels
What are the general clinical signs of canine leishmaniasis?
May not show signs until months or years after exposure
Bimodal distribution pattern: usually <3 years or >8-10 years
Most dogs present with poor BCS/cachexia and anorexia
- esp with visceral leishmaniasis in pancreas, spleen, and/or bone marrow
Main skin signs include nodules, ulcers, and pustules, and exfoliative dermatitis
Ocular damage, coagulation disorders, splenomegaly, bone marrow, etc
Lymphadenopathy is not correlated with parasite load or clinical state
What are the cutaneous signs of canine leishmaniasis?
Main skin signs include nodules, ulcers, and pustules, and exfoliative dermatitis
- Alopecia, pale mucosa, and erythema are common
- Often causes onychogryphosis
- Silvery white asbestos like scaling
- Mostly on head, pinnae and extremities +/- generalized
- Nasodigital hyperkeratosis, alopecia, periocular alopecia (lunettes)
- nasal depigmentation with erosion
Associated with lichenoid/interface dermatitis in absence of parasites
May get lesions are pressure points
- potentially because infected cells are transported there when injured
Why do dogs with leishmaniasis often have splenomegaly ?
presence of amastigotes and to the macrophage infiltration
- spleen is one of the most affected organs (skin and bone marrow too)
spleen concentrates high parasite burden and has morphological changes
- hypertrophy and hyperplasia of the red pulp
- infiltration of mononuclear and plasma cells
- hypertrophy and hyperplasia of white pulp trying to make more macs
In which organ is the response to Leishmania established for dogs and the process of cell activation occurs?
The spleen
Which TLRs play a role in splenic innate immunity during canine leishmaniasis infections?
TLR-5 and TLR-9
In which organ is responsible for the persistence of the disease including relapses for Leishmania in dogs?
bone marrow (a densely parasitized organ)
- hematopoiesis in early stage –>
- pancytopenia, non-regenerative anemia, histiocytic hyperplasia –>
- ending in medullar aplasia
translate into haematological and coagulation disorders
What is the correlation between cutaneous parasite load, disease severity and vector infectivity in canine Leishmaniasis?
Skin parasite load (though variable) seemed to increase with disease severity
Parasite load is correlated with the vector infectivity
- some may be super-spreaders
Why do dogs with leishmaniasis often have hepatomegaly?
In the liver it establishes itself in Kupffer cells
- formation and maturation of granulomas
- removes pathogens and their antigens from the circulation
Can progress to hepatitis
What is resistance to canine leishmaniasis associated with?
higher levels of total T lymphocytes (CD4+ and CD8+) and CD21+ B cells
- converse for increased susceptibility
strong lymphoproliferative response of PBMCs to Leishmania antigen
How do you diagnose canine leishmaniasis?
PCR
- rtPCR is preferred because it can be converted into quantitative PCR
- may have best results lymph node or bone marrow
- can also do biopsies, blood, conjunctival, and oral swabs, and hair
indirect fluorescent antibody test (IFAT) - considered “serologic gold standard”
- good in Chagas disease-free areas
- variable time to antibody production but titers usually high if sick
- pair with another test (can’t always differentiate between exposure and disease)
ELISA
- ELISA usually uses Q antigen and kinesin-derived antigens (ex. rK39)
Cytology especially of the bone marrow or lymph node (or FNA)
- 52–85% sensitivity for bone marrow
- 52–58% sensitivity for lymph node aspirates
Histopathological and IHC
Culture base on blood agar
- difficult and takes a month to determine if negative
- grows in 64–100% of cases
Xenodiagnoses
What species get leishmaniasis?
Humans, dogs > cats, horses and other domestic animals (ex. sheep and cattle)
What is the structure of a Leishmania amastigote?
circular or oval in shape, 2-4 mm in diameter, and contain around, basophilic nucleus and a small, rodlike kinetoplast
- inside of macrophages
- best seen with Giemsa stain
What is the most common species of Leishmania seen in horses?
Americas: L. braziliensis
Europe: L. infantum
What are the histopathologic findings associated with cutaneous Leishmania?
Lymphohistiocytic/(pyo)granulomatous inflammation with vasculitis
- +/- hyperkeratosis
9 histopath patterns noted w this variable dz
Destroys sebaceous glands (causes exfoliative dermatitis)
2-4 um organisms, round basophilic nucleus and rodlike kinetoplast
Visible with routine stains, Giemsa is the best
What do PCR primers typically target when testing for Leishmania?
minicircle kinetoplast DNA and internal transcribed spacer 1 ribosomal DNA
What is xenodiagnosis?
involves feeding a suspected infected host to an intermediate host, such as an insect, and then examining the intermediate host for the presence of parasites
What is the treatment for canine leishmaniasis?
Usually includes allopurinol, antimonials, miltefosine
- antimonials are meglumine antimoniate and sodium stibogluconate
- antimonials have been replaced by amphotericin B in some places for humans
- widespread resistance to meglumine antimoniate
Consider treatment based on severity of disease
- mild disease: allopurinol alone
- moderate to severe: allopurinol + antimonials/miltefosine
Monitor treatment at 1 mo, 3-4 mo, and then every 6-12 mo
- Antibody titer can be used to anticipate relapses
Other medications to consider
- the aminoglycoside paromomycin/aminosidine
- domperidone
- fluroquinolones (increase killing by macrophage)
- pentamidine
- spiramicin
- metronidazole
- ketoconazole
What is allopurinol resistance in Leishmania associated with?
decrease in S-adenosylmethionine synthetase copy numbers
What is the prognosis for canine leishmaniasis?
Complete elimination is very difficult
- relapses are common
- parasite load can be decreased to asymptomatic levels with chemotherapy
- in some areas, culling is recommended
What is the dominant sterol in the Leishmania cell membrane?
ergosterol
What is the effect of miltefosine on proteinuria in dogs with leishmaniasis?
decrease proteinuria
What are ways to prevent canine leishmaniasis?
Insect repellant (deltamethrin and permethrin)
Keeping animals in at dawn and dusk
Vaccination in some locations (4 licensed)
- creates differential isotype humoral immune response
- not super reliable for telling the difference
What are the typical clinical signs of cutaneous leishmaniosis in horses?
Lesions are usually multiple
commonly on muzzle, periocular, pinnae, axillae, groin, scrotum, legs, and neck
papules and nodules, 5-20 mm in diameter
- can become alopecic, crusted, and ulcerated
- neither pruritic nor painful
horses are typically otherwise healthy
many horses undergo spontaneous remission within 3-5 months
Is serology a good way to test for Leishmania in horses?
Not reliable
Antileishmanial antibodies are typically absent or present at very low titers in serum
What morphologic features can you use to tell ticks apart?
Scutum (shield made of chitin)
Mouthparts (palps and toothed hypostome)
Festoons (short grooves located on the back margin)
- lacking in Ixodes
Adult male American Dog Tick (Dermacentor variabilis)
Adult female American Dog Tick (Dermacentor variabilis)
What is the lifestyle of the American Dog Tick (Dermacentor variabilis)?
3-host lifecycle (use 3 different hosts in their lifecycle)
- Larvae and nymphs mainly infest small mammals
- Adult stages prefer medium-sized hosts
found over most of North America
Most active April-early August
predominantly along forest edges and in areas with little or no tree cover
can transmit Rocky Mountain Spotted Fever and Tularemia
Why are ectoparasites rare in chinchillas?
Their dense haircoat
What are the important mites in ferrets?
Psoroptidae: Otodectes cynotis
Sarcoptidae: Sarcoptes scabiei
What are the important ticks in ferrets?
Ixodes ricinus
What are the important insects in ferrets?
Fleas
What are the important helminths in ferrets?
Hypoderma spp.
Cuterebra spp.
Dracunculus insignis.
What are the important ectoparasites in gerbils?
Demodex meroni
fur mite Acarus farris
What are the important mites in guinea pigs?
Sarcoptidae – *Trixacarus caviae and Sarcoptes scabiei
Atopomelidae – Chirodiscoides caviae
Myocoptidae – Myocoptes musculinus
Cheyletiellidae – Cheyletiella parasitovorax
Demodicidae – Demodex caviae
What are the important lice in guinea pigs?
Gliricola porcelli
Gyropus ovalis
What are the important mites in hamsters?
Demodex criceti
Demodex aurati
Notoedres notoedres
Notoedres cati
Sarcoptes scabiei
Trixacarus caviae
Ornithonyssus bacoti
What are the important insects in hamsters?
fleas - C. felis felis
What are the important mites in hedgehogs?
Caparinia tripilis.
Sarcoptes spp.
Otodectes spp.
Notoedres spp.
Chorioptes spp.
Demodex erinacei.
Trombicula autumnalis.
What are the important ticks in hedgehogs?
Ixodes hexagonus, Ixodes ricinus, Ixodes trianguliceps.
What are the important insects in hedgehogs?
Flies – Lucilia, Calliphora.
Fleas – Archaeopsylla erinacei.
What are the important mites in mice?
Myobidae – fur mites Myobia musculi, Radfordia affinis.
Myocoptidae – mange mites Myocoptes musculinus, Trichoecius rombousti
Dermanyssidae – Liponyssoides sanguineus, Dermanyssus gallinae.
Psorergatidae – Psorergates muricola.
Demodicidae – Demodex musculi.
What are the important insects in mice?
Lice.
- Polyplax serrata.
Fleas.
- Xenopsylla spp.
- Nosopsylla spp.
What are the important endoparasites in mice?
Pinworm (Syphacia obvelata)
What are the important ticks in rabbits?
Haemaphysalis leporis-palustris
What are the important mites in rabbits?
Listrophoridae – Leporacarus gibbus.
Psoroptidae – Psoroptes cuniculi.
Cheyletiellidae – Cheyletiella parasitovorax.
Psorergatidae – Psorobia lagomorphae.
Demodicidae – Demodex cuniculi.
Sarcoptidae – Notoedres cati, Sarcoptes scabiei.
Trombiculidae – Neotrombicula autumnalis.
Notoedres
What are the important mites in rats?
Myobidae – Radfordia ensifera.
Sarcoptidae – Notoedres muris, Sarcoptes scabiei var. cuniculi, Trixacarus diversus,
Trixacarus caviae.
Dermanyssidae – Liponyssoides sanguineus.
What are the important insects in rabbits?
Lice.
– Haemodipsus ventricosus.
Fleas.
– Spillopsyllus cuniculi.
– Ctenocephalides felis and canis
– Cediopsylla simplex.
– Odontopsyllus multispinous.
– Echidnophaga gallinacea.
Green bottle fly (Lucilia spp) myiasis
What are the important insects in rats?
Lice – Polyplax spinulosa (the spined rat louse).
What are the important endoparasites in rats?
Pinworms (Syphacia obvelata)
What are the most important mites in caged birds?
Burrowing skin mite: Cnemidocoptidae (C. pilae), Epidermoptidae. (Myialges)
Surface skin mite: Dermanyssidae (D. gallinae), Ornithonyssus spp.
Feather mites Protolichus lunula and Dubininia melopsittaci
Quill mites (Syringophilidae)
What are the most important mites in raptors?
Burrowing skin mite – Cnemidocoptidae (C. pilae).
Surface skin mite – Dermanyssidae (D. gallinae), Ornithonyssus spp.
Feather mites.
Quill mites.
What are the most important ticks in raptors?
Ixodes ricinus
What are the most important insects in raptors?
Lice.
Blow flies.
Louse flies/Keds.
Mosquitos.
Beetles.
Which parasites can migrate into subcutaneous tissue in snakes?
Cestode, Spirometra.
Trematodes, Spirorchidae.
Spirurids.
Pentastomids are zoonotic
What are the most important ectoparasites in snakes?
Helminths. (Dracunculus)
Filarioidae
Mites. (Ophionyssus natricis)
Ticks. (Aponomma transversale)