Protozoan Parasites: Lecture 21 Apicomplexans 3 Heteroxenous Coccidia - Part 1 Pages 37-49

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Protozoan Parasites: Lecture 21 Apicomplexans 3 Heteroxenous Coccidia - Part 1 Pages 37-49

Tissue cyst -forming Coccidia General Taxonomy Apicomplexa Heteroxenous Two host life cycles Asexual & sexual reproduction Intestinal epithelium or subepithelium of a carnivore definitive host Asexual development also takes place in extra-intestinal tissues of the intermediate host Tissue cysts - forming coccidia

General Morphology Intestinal stages Same as for other coccidia merozoites, microgamonts, macrogamonts

General Morphology Extra-Intestinal stages General coccidian zoite morphology Tachyzoites Crescent shaped, ~6 µm Proliferate rapidly forming colonies Bradyzoites Crescent shaped, ~7 µm Multiply slowly within tissue cysts Tachyzoite on blood smear Bradyzoite within tissue cyst

General Morphology Extra-Intestinal stages Tissue cysts Contain bradyzoites which divide slowly resulting in increasing sizes of tissue cysts Young tissue cysts 5 µm Older tissue cysts grow to 50 µm

Toxoplasmosis Toxoplasma gondii World wide distribution Definitive host Cats & other felids Intermediate host Indiscriminate Any warm blooded animal mammals or birds

Dubey 1998 Toxoplasma gondii: Life Cycle Few oocysts Produced from ingesting tachyzoites 20% of cats ingesting oocysts develop a patent infection - few oocysts Cats Ingesting bradyzoites produce millions of oocysts = most important mode of transmission to definitive host 1-5 days to mature = sporulate

Jones et al. 2003

Prevalence Cats: North America ~ 30% Spain ~ 45% Japan ~ 6% Humans: North America - 15-23% Veterinary staff (Ontario 2002) - 14.2% U.K. - 30% France - 80% New Zealand - 60% BUT all are dropping Other animals: Variable seroprevalences

Pathogenesis & Clinical signs Cats - definitive host Intestinal phase Young cats Shed oocysts - intense & brief No pathology, no clinical signs Extra-intestinal phase Kittens (< 3 months) Rarely in older cats Common clinical signs - Anorexia, depression, lethargy, icterus, vomiting Less common signs pneumonia, encephalitis & chorioretinitis Death in severe cases (rare)

Pathogenesis & Clinical signs Intermediate hosts Two types of disease: Acquired Toxoplasmosis Congenital Toxoplasmosis

Acquired Toxoplasmosis Domestic animals Sheep & Goats Mild febrile response Cattle & Horses Clinical signs rare Swine Clinical signs rare Dogs Clinical signs rare BUT when occur Young dogs <1 year old Myositis & muscle atrophy CNS signs - ataxia, tremors, uveitis

Acquired Toxoplasmosis Humans Zoonosis Healthy people: Most have no clinical signs Mild clinical signs Flu-like symptoms Transient headache, muscle & joint pain, fatigue, swollen lymph nodes Once infected forever protected But this may not be true anymore

Acquired Toxoplasmosis Humans Zoonosis Immunodeficient people: Severe disease Pneumonia, myocarditis, encephalitis, chorioretinitis, fatigue, swollen lymph nodes Reactivated latent infection...

Congenital Toxoplasmosis Most serious form of disease Major concern Humans Sheep > goats Primary maternal infection acquired during pregnancy for transmission to placenta / fetus

Congenital Toxoplasmosis Sheep > Goats Major cause of abortion Fetus may be mummified, macerated, autolyzed or resorbed Fetal lesions in heart, brain & liver

Congenital Toxoplasmosis Sheep > goats Focal inflammation & necrosis within the placenta Small (~2 mm) white chalky lesion Tachyzoites & tissue cysts Subsequent pregnancy Abortions are rare Ewe develops immunity Normal pregnancy

Congenital Toxoplasmosis Humans Zoonosis Abortion rare Premature birth common At birth: Classic triad Later in life Chorioretinitis, hydrocephalus, intracranial calcification Mental illness, blindness, epilepsy... Asymptomatic No clinical signs Reactivated latent infections...

Diagnosis Definitive host: Cats Centrifugal Fecal flotation Cats shed oocysts sporadic & inconsistent confounders Hammondia & Besnoitia sp. Toxoplasma Reference Lab ELISA & PCR

Diagnosis Serology Valuable in Humans > Sheep but less value in cats Cats Acute infection Elevated IgM titres with low/normal IgG Greatest risk to shed oocysts Chronic/Previous infection Low IgM titres & higher IgG Less likely to shed oocysts Assessing human health risk Seronegative cat: not likely currently shedding but will shed if exposed. This cat is the greatest risk to human health. Seropositive cat: probably not shedding oocysts (see above acute vs. chronic) & is less likely to shed oocysts if re-exposed or immunosuppressed. Still recommended that potential exposure to oocysts (infected intermediate hosts) be minimized.

Toxoplasmosis Treatment Humans Congenital Mother & child Acquired / Reactivated Immunodeficient Pyrimethamine & sulphadiazine &/or spiramycin with folinic acid Animals Rare to treat livestock Common to treat companion animals Pyrimethamine & sulphadiazine, clindamycin, azithromycin

Prevention & Control Cats : Prevent hunting & scavenging Keep cats indoors Do not feed raw or undercooked meat &/or unpasteurized dairy Seronegative cat is a risk to humans if infected Seropositive cat less risk to humans Unless shedding now = risk If not shedding = less risk Domestic Animals: Prevent cats defecating in feed & water Control cat population on farm Toxovax in sheep / goats One dose = lifetime protection (New Zealand & UK)

Prevention & Control Humans Zoonosis What can you do? Do not eat meat Uncooked or rare Pasteurized dairy products only Empty litter box daily - gloves, spouse? Gardening - wear gloves Wash vegetables & fruit Proper hygiene hand washing Starting a family? Contact you health professional and have a conversation Remember Dogma of Once infected forever protected may not be true anymore

?

Neosporosis Neospora caninum Fatal neuromuscular disease of dogs Major cause of reproductive failure & abortion in cattle

Morphology All stages identical to Toxoplasma except the tissue cysts Neospora tissue cysts are found only in the CNS, peripheral nerves & retina Toxoplasma tissue cysts thin walls (< 1 µm) Neospora tissue cysts thick walls (>1 µm & up to 4 µm)

Neospora life cycle 1 2 & 3 4 # s correspond to clinical signs, please see later slides 41-43

Epidemiology Transmission Percentage of dogs/canids shedding oocysts is unknown Congenital transmission occurs in dogs, cattle, sheep, goats, pigs, horses cats, mice, monkeys...birds too! No evidence of zoonosis Repeated congenital transmission may occur & can occur over several generations

Prevalence Common cause of abortion in beef & dairy cattle worldwide Serologic surveys cattle Up to 100% of cattle have been exposed in some herds Maritime dairies - 73% of herds & 19% of cows found to be positive UK ~ 35% of abortions Epidemiology

Epidemiology Prevalence Seroprevalence in dogs Variable Higher rates in dogs on dairy farms vs. dogs from urban areas Most clinical cases occur in congenitally infected young dogs

Pathogenesis Similar to toxoplasmosis Destruction of host cells by tachyzoites resulting in focal areas of necrosis Focal encephalitis, encephalomyelitis, myositis & myocarditis characterized by necrosis & non-suppurative inflammation http://www.visionveterinaria.com/ri vep/art/09jun43.htm

Clinical signs Cattle Abortion is major clinical sign (2) Cows of any age can abort between 3 months gestation & term Most abortions around 5-6 months Fetus may die in utero, be resorbed, mummified, autolyzed or stillborn

Clinical signs Cattle Infected calves born alive (3) Neurological signs Ataxia, decreased patellar reflexes & exophthalmia Underweight, downer, hind limbs &/or forelimbs flexed or hyper extended

Clinical signs Cattle Calves may also be born infected without clinical signs (1) Persistent infection Risk to next generation Calves may also be born free of infection (4) Cycle is broken

Clinical signs Neosporosis in Dogs Subclinical infection is common Clinical disease Young dogs 3 weeks to < 6 months Rigid hyper-extended limbs & hind limb paresis - paralysis Paralysis of the jaw with difficulty swallowing Muscle flaccidity, muscle atrophy, heart failure Severe dermatitis Worst case - all above + cervical weakness, dysphagia, megaesophagus...death Litter mates are often infected Older dogs less common

Diagnosis Cattle Fetal tissues - brain, heart, liver, lungs Tissue cysts Lesions Focal areas of necrosis Non-suppurative inflammation Immunohistochemistry IHC Neospora vs. Toxoplasma tachyzoites Fetal fluids & serum of cows Antibody titre - IFAT, ELISA, DAT http://www.visionveterinaria.com/ rivep/art/09jun43.htm

Diagnosis Dogs Antibodies - serum or CSF Litter mates with clinical signs Congenital neosporosis Gross lesions Ulcerative dermatitis Necrosis of CNS Yellowish-white streaks in muscles IHC, ELISA...? Centrifugal Fecal flotation Sporadic & inconsistent shedding confounder species Hammondia &Toxoplasma

Treatment & Control Cattle Protect feed & water sources from contamination Do not let dogs eat fetal membranes, fetuses or dead calves Cow that aborts once may abort again (persistent infection) & may have to be culled No treatment for livestock Vaccine but no efficacy data?

Treatment & Control Dogs Prevent canids from eating fetal membranes, fetuses or dead calves by proper disposal Treatment may be attempted with sulfonamides, pyremethamine & clindamycin Treat all littermates No therapy to Tx doggie mothers to prevent transmission

VPM-122 Midterm Exam # 3 Thursday, March 23, 2017 Lecture 286A N/286B N/286C N/287N 0830-0920H Covers my lectures (#17-22) Lecture 23 is a review (20/03/2017) Protozoan Parasites lecture notes pages, 1-54. Format Multiple choice, short answer & essay Point form is okay for answers...including the essay!!!!! Say no to drugs & no drug names on exam either! No prevalence numbers