Diane Hendrix, DVM, DACVO Professor of Ophthalmology
Diane Hendrix, DVM, DACVO Professor of Ophthalmology University of Tennessee Toxoplasma gondii Neospora caninum Encephalitozoon cuniculi Toxoplasmosis Toxoplasma gondii Affects most warm-blooded animals Obligate intracellular protozoa The cat is the definitive host
cmgm.stanford.edu/.../boothroydlabdesc.html Toxoplasmosis
Asexual life cycle
Animals (including cats)→ ingest bradyzoites → transform to tachyzoites → penetrate intestinal mucosa → spread throughout the body → cause disease → encyst and become bradyzoites Toxoplasmosis Sexual life cycle Limited to the cat In cats →ingestion of bradyzoites → transform to tachyzoites → penetrate intestinal mucosa → start intra-epithelial cycle of sexual proliferation →oocysts →shed in the feces Toxoplasmosis
Immunity
Tissue damage
Cellular immune memory
T-cell mediated immunity
IgM, IgG, IgA and IgE are produced against both the membrane and intracellular proteins. Toxoplasmosis
Ocular disease in humans Reactivations of congenitally acquired infection Retinitis is pathognomonic Anterior uveitis is rare
Progress in Retinal and Eye Research 39 (2014) 77e106 Toxoplasmosis
Congenital disease in humans Hydrocephalus Intracranial calcification Chorioretinitis Toxoplasmosis
Disease in cats
Clinical signs vary
In adults illness is usually subclinical. Toxoplasmosis
In kittens, tachyzoites spread systemically & cause: Interstitial pneumonia Myocarditis Hepatic necrosis Meningoencephalomyelitis Chorioretinitis Lymphadenopathy Myositis Immunocompromised adult animals are susceptible to developing acute generalized toxoplasmosis. Toxoplasmosis
Ocular lesions in cats
Multifocal chorioretinitis Anterior uveitis Optic neuritis Histopathology Toxoplasmosis
The role of toxoplasmosis in causing anterior uveitis in cats without systemic illness is controversial. Toxoplasmosis
Disease in dogs Infection via ingesting sporulated oocysts ingestion of tissue cysts in infected meats ingestion of a transport host congenital transmission
Usually sub-clinical Clinical signs may include neuromuscular, respiratory, or GI disease. Systemic disease is relatively rare Ocular toxoplasmosis in dogs
Clinical signs Histopathology
Infrequent Mononuclear cell anterior uveitis* Anterior uveitis Hyperplasia of the ciliary epithelium Vitritis Pseudocyst of ciliary epithelium Chorioretinitis without inflammation Extraocular/polymyositis Protozoa Scleritis Optic neuritis Toxoplasmosis
Diagnosis
Isolation Histologic identification Serologic evaluation C value of >8 PCR
Treatment
Clindamycin Neosporosis Neospora caninum Coccidian protozoal parasite Similar to T gondii Found worldwide Neosporosis
Transmission
Dogs (coyotes) are the definitive host
Intermediate hosts are dogs, deer, cattle and other herbivores
Transplacental transmission occurs Neosporosis
Disease in other species
Major cause of abortion in cattle (and other herbivores)
Infection in cattle can cause exophthalmia.
Wild mammals may be a reservoir for infection in cattle. Neosporosis
Disease in dogs Older dogs (less common) Multifocal CNS involvement Polymyositis Myocarditis Hepatitis Dermatitis Horner’s syndrome (one report)
Transplacental infection Nonsuppurative encephalitis Severe myositis Hind limb paralysis Neosporosis
Ocular disease Seen in dogs with CNS disease Chorioretinitis Mild anterior uveitis Optic neuritis Extraocular myositis Encephalitozoon cuniculi
Obligate intracellular microsporidium Wide host distribution Primarily affects rabbits Opportunistic in immunocompromised humans Eyes, CNS, and kidneys are predilection sites Encephalitozoon cuniculi
Pathogenesis
Sporulating eukaryotic protozoa Infective spores are shed in the urine. The spore survives in the environment and is the transmissible agent. Infection has occurred via intravenous, intracerebral, oral, nasal, and rectal routes and vertical transmission. Dwarf rabbits and NZW may be more susceptible. Encephalitozoon cuniculi
Clinical disease in rabbits
Phacoclastic uveitis
Cataracts Whitish/yellowish intraocular masses (granulomas) Anterior uveitis Hyperemia Unilateral Encephalitozoon cuniculi
Other clinical disease in rabbits
Granulomatous encephalitis Nephritis with kidney failure
Typical disease pattern is a subclinical, chronic, persistent infection. Encephalitozoon cuniculi
Diagnosis
Histopathology and demonstration of organisms is required to confirm infection.
Tentative diagnosis made on clinical signs in combination with serological testing. Encephalitozoon cuniculi
Treatment for Phacoclastic Uveitis phacoemulsification steroids have little to no effect fenbendazole PO QD enrofloxacin or oxytetracycline may be used in rabbits showing neurological signs +/- corticosteroids Encephalitozoon cuniculi
Prognosis
Rabbits with phacoclastic uveitis do not show other symptoms and survive. ½ the rabbits with neurological signs recover
Those with kidney failure die Encephalitozoon cuniculi
Histopathology (Ocular) Pyogranulomatous infiltration Zonal inflammatory pattern The anterior uvea is relatively spared Organisms are only found within liquefied lens cortex Microsporidia are apparent with silver stain and are Gram + and acid-fast Immunohistochemistry
Encephalitozoon cuniculi
Disease in Cats
Diagnosed in several cats Median age 3.5 years Most bilateral Cataracts varied from incipient to mature Treated with phaco and fenbendazole Diagnosed on histopath and PCR Encephalitozoon cuniculi
VO pp 37-47, 16 SEP 2011 Encephalitozoon cuniculi Other species Blue fox - cataracts Mink - cataracts Humans develop keratoconjunctivitis, keratitis, uveitis and endophthalmitis. Snow leopard
Vet Ophthalmol. 2015 Jan;18 Suppl 1:143-7 Parasitic flagellates Trypanosoma sp. Cryptobia (T.) salmositica Leishmania infantum
jcs.biologists.org/.../issue12/cover.shtml Trypanosomiasis
Trypanosoma sp. Hemoflagellate protozoan Transmitted by the tsetse fly Flies inoculate the skin
web.indstate.edu/.../parasitology/PROTOZHO.HTM Trypanosomiasis
Immune complexes cause inflammation
When antibodies are made against the surface- coat glycoproteins the trypanosomes die.
Trypanosomes have multiple genes that code for different surface-coat glycoproteins that are not vulnerable to the immune response resulting in persistence of the organism. Trypanosomiasis
Disease in dogs and cats
Trypanosoma brucei
corneal opacification
ciliary body cysts may contain organisms
The disease occurs in Africa
http://pathmicro.med.sc.edu/parasitology/blood-proto.htm Trypanosomiasis
Disease in dogs and cats Trypanosoma evansi
corneal opacities
conjunctivitis
blepharitis
anterior uveitis
endophthalmitis
transmitted by biting flies
North Africa, the Middle East, Asia, the Far East, and Central and South America http://congohounds.gorillacd.org/2012/04/08/bloodhound-teams-learn-to-deal-with-common-nuisances-tsetse-flies-and-trypanosomes/ Trypanosomiasis Disease in livestock Sub-Saharan Africa, Asia Histologic examination and South America trypanosomes in the Relapsing hypopyon fibrin of the anterior chamber and anterior Eyelid edema uvea mononuclear inflammatory infiltrate Aqueocentesis may demonstrate
www.uoguelph.ca/~pwoo/animaltryp.jpg trypanosomes Salmonid cryptobiosis
Hemoflagellate, Cryptobia salmositica
Transmitted by leeches (Piscicola salmositica)
Direct transmission
www.uoguelph.ca/~pwoo/animaltryp.jp Salmonid Cryptobiosis
Clinical signs Anorexia Exophthalmia Splenomegaly Hepatomegaly General edema Abdominal distention with ascites Microcytic and hypochromic anemia, and red cells give a positive antiglobulin reaction. West coast of North America
www.uoguelph.ca/~pwoo/animaltryp.jp Leishmaniasis geo.arc.nasa.gov/.../diseases/images/leish.gif Flagellate organism Leishmania infantum Endemic on Mediterranean shore and in parts of east Africa, India, and Central and South America. +/- USA Domestic and wild members of Canidae serve as reservoir hosts Intermediate host, a sandfly (Phlebotomus spp.), is also found in USA Ocular signs
Arq. Bras. Med. Vet. Zootec. vol.58 no.5 Belo Horizonte Oct. 2006 Leishmaniasis
Systemic signs Lymphadenopathy Splenomegaly Hepatomegaly Renal failure Anemia Thrombocytopenia Muscular weakness Cachexia www.liv.ac.uk/.../issue18/images/W046387R.jpg Abnormal locomotion Varying non-pruritic dermatologic conditions Leishmaniasis
Histopathology
Vasculitis and intense inflammatory zones
Amastigotes are seen in the ciliary processes, ciliary body, limbus, lacrimal duct and histiocytes. Leishmaniasis
Diagnosis and Treatment
ID on histopathologic or immunoperoxidase evaluation of biopsies
ELISA and IFA
PCR
Allopurinol Leishmaniasis
Disease in cats
Conjunctivitis Blepharitis Keratitis Amastigotes are found within macrophages and giant cells Other Parasitic Infections
Habronemiasis
Ocular filariasis
Ocular larval migrans
Ophthalmomyiasis
Cuterebra
Vet Parasitol. 2015 Feb 28;208(1-2):84-93 Habronemiasis
Parasite of the equine stomach
Draschia megastoma Habronema muscae Habronema microstoma
Adults are 13 mm to 25 mm long
Normal life cycle goes through the stomach Cutaneous Habronemiasis Initial rapid production of granulation tissue Does not resolve during fly season Sulfur granules Severe pruritus Habronema conjunctivitis Ulcerated nodules Contain caseo-calcareous foci Located near the medial canthus Tend to abrade the cornea Habronemiasis Treatment
Surgical removal if irritating Ivermectin is the treatment of choice Fenbendazole
Habronemiasis
Adult dromedary camel Non-healing, severely pruritic, ulcerative fibrotic plaque Degenerating nematode larvae within eosinophilic granulomas Treatment
repeated debridement injectable ivermectin anti-inflammatory therapies injectable and topical antibiotics
Veterinary Dermatology, 21, 527–530 Habronema in a rhino
A captive female square-lipped rhinoceros Intermittent signs of bilateral conjunctivitis and conjunctival proliferation Treatment with antibiotics and glucocorticosteroids was ineffective, as were repeated dewormings. Biopsies in 2000 & 2006 only showed eosinophils in 2006 After progression to vision loss aggressive resection was done. 2013 biopsy showed severe allergic conjunctivitis, eosinophilic granuloma, and habronematid (Habronema or Draschia) larval infection. VO 28 MAR 2015 DOI: 10.1111/vop.12269 Ocular nematodiasis
Intraocular nematodiasis is infrequent
Includes two distinct conditions
ocular filariasis
ocular larval migrans Ocular filariasis aberrant migration of immature Dirofilaria immitis dogs and humans +/- concurrent microfilaremia ocular signs result from aberrant migration German Shepherds may be predisposed Ocular involvement is unilateral
Worm is usually in AC
Anterior uveitis (signs worsen with exam) Severe corneal edema Mild to severe corneal opacity Uveitis
Antigen-antibody complex formation may play a role
Typically, one 5- to 10-cm filaria is seen undulating in the anterior chamber
Light stimulation increases motility of the filaria Prognosis for nematodiasis
Favorable with anti-inflammatory therapy and manual removal of the filaria.
Presurgical adulticide therapy is not advised
Microfilaricide administration causes increased activity of the filaria and transient exacerbation of clinical signs in one case Angiostrongylus vasorum
Metastrongylid nematode Anterior chamber of dogs Primarily found in Europe Migrating larvae may become aberrant Severe granulomatous uveitis and secondary glaucoma may result Infection may also manifest as a free nematode in the anterior chamber Mid East Afr J Ophth. 2014;21:312-6. doi: 10.4103/0974-9233.142267. Ocular larval migrans
Aberrant ocular migration of Toxocara spp. T. canis is most commonly involved Public health significance, as the nematode causes OLM and VLM in children Aberrant migration L3 form which typically migrates to the lung from the stomach aberrantly migrates to the eye Toxacara has propensity for the eye Balisascaris is neurotrophic OLM causes inflammation primarily of the retina and vitreous
Image and text copyright © Dennis Kunkel Ophthalmoscopy Hyperreflectivity Hyperpigmentation Vascular attenuation Small, solitary focal granulomas Orbital cellulitis Rare anterior uveal involvement
http://cueflash.com/decks/17_-_Nematodes http://www-ncbi-nlm-nih- gov.proxy.lib.utk.edu:90/pubmed/146 41832# Onchocerciasis
http://www.mectizan.org/lifecycle.asp Onchocerciasis
Disease in dogs
O. lupi
Acute ocular signs
Chronic ocular signs
Granulomatous nodules Masses in the conjunctiva, nictitans, and sclera Uveitis Periorbital swelling Exophthalmos Onchocerciasis Onchocerciasis VO 2015 DOI: 10.1111/vop.12277 characteristic ridges on the cuticle Greece Parasit Vectors. 2015 Feb 8;8:89 Vet Parasit, Vol 203, 1–2, 2014, 91–95 asymptomatic dog pos on skin snip test. Onchocerciasis
Disease in horses
Small (<1 mm), raised, white nodules Depigmentation temporal bulbar conjunctiva Corneal edema and punctate/streaking opacities of the stroma May be an association with the microfilariae and ERU Onchocerciasis Histopathology
Pyogranulomatous nodules with eosinophils
Lymphoplasmacytic uveitis
Microfilariae in the uteri of females
Can be isolated from skin biopsy specimens Onchocerciasis
Histopathology Onchocerciasis
Treatment
No treatment is effective against the adults.
Ivermectin and moxidectin - microfilarae Disease in cats
Orbital disease Western US Posterior episcleral parasites No suspicion of disease O lupi Onchocerciasis River Blindness Onchocerca volvulus
Photo credit: WHO/TDR/OCP Ophthalmomyiasis Aberrant ocular migration of fly larvae Order Diptera Ophthalmomyiasis externa Ophthalmomyiasis interna anterior Ophthalmomyiasis interna posterior Ophthalmomyiasis
Thought that fly larvae cross the conjunctival surfaces Seen as an incidental finding Can be found in the acute stages with uveitis Diagnosis visualization of the larvae in the anterior or posterior segments wandering tracks in the fundus Ophthalmomyiasis
Ophthalmomyiasis interna posterior Dogs, cats, and humans Characteristic lesion is road- map-like subretinal tracts that may be active or inactive Active disease may be associated with uveitis, retinal detachment, and hemorrhage The larva may be visible in active infections Ophthalmomyiasis
Treatment
Inactive infections require no therapy
Active disease
Anti-inflammatory therapy Organophosphates The larva may spontaneously depart Physical removal of the larvae from the anterior chamber Laser therapy or killing the larvae while in the eye is not recommended Man with pain in left eye. Ophthalmomyiasis from the sheep nasal bot fly, Oestrus ovis. Endemic in Isreal.
Ann Emerg Med. 2015 Jun;65(6):e7-8.
VO 17, 6, pages 448-453, 3 SEP 2014 DOI: 10.1111/vop.12210 Can J Ophth 46;6, 2011, 553–554 external ophthalmomyiasis caused by Lucilia sericata Meigen (Diptera: Calliphoridae)--a green bottle fly.
J Infect Dev Ctries. 2014 Jul 14;8(7):925-8. doi: 10.3855/jidc.4552 Anterior spiracles, mental, phy issues Serbia Thelaziasis
Found multiple species. •http://path.upmc.edu/cases/case279/images/fig01a.jpg
Western USA, Europe and southeast Asia
Lateral serrations of the cuticle cause mechanical damage Milky-white worms ~ 10-14 mm long Thelaziasis
Life Cycle
1st stage larvae are ingested by flies
Then after undergoing 2 molts, the 3rd stage larvae are transferred back to the eye when the fly feeds.
Adults live under the eyelids or behind the nictitans Thelaziasis Dogs
T. callipaeda and T. californiensis Clinical signs Unilateral or bilateral purulent conjunctivitis Blepharospasm Epiphora Conjunctivitis Keratitis
Intense lacrimal Calero-Bernal 2014 secretion
Dr. Rebecca Burwell T. californiensis
North America Dogs, mule deer, and others. The vectors are Musca spp. and Fannia spp. Increased international trade and travel Thelaziasis
Dogs
Treatment
Topical levamisol (2% aqueous solution) SQ ivermectin Physical removal of the nematodes Prophylactics – spot on formulation vs collar Cats
Vet Parasitol. 2014 Jul 14;203(3-4):287-93 Thelaziasis
Horses and Cattle
Horses - T. lacrymalis Cattle - T. gulosa, T. skrjabini, and T. rhodesii Thelaziasis
Horses and Cattle
Lacrimal glands and ducts
Superficial locations on the cornea, in the conjunctival sac, and under the eyelids and nictitating membrane.
Worms may also be found on the periorbital hair or skin during anesthesia or following migration after death of the host. Thelaziasis
Horses and Cattle
Often asymptomatic
Invasion of the glands and ducts may cause inflammation and necrotic exudation.
Conjunctivitis and blepharitis are common.
Keratitis may develop in severe cases, particularly with T. rhodesii infections in cattle.
Subconjunctival cysts may also develop in cattle.
Thelaziasis
Diagnosis
Gross inspection of the eyes (esp for T. rhodesii)
Others tend to be more evasive
Topical anesthetics allow for tissue manipulation
Microscopic examination of tears for embryonated eggs or larvae may be done
Parasitic Metazoans Cysticercosis is a zoonotic disease caused by the larval form of Taenia solium, the pork tapeworm. Swine are the natural intermediate host The larval stage may invade the eye and orbit of various species Causes orbital and ocular http://www.bhj.org/journal/2002_4404_oct/case_693.htm5 cysts