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 sub- epithelium 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

Bradyzoite within tissue cyst

Tachyzoite on blood smear

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

Toxoplasma gondii: Life Cycle

1-5 days to mature = sporulate

Cats Ingesting bradyzoites produce millions of oocysts = most important mode of transmission to definitive host

Few oocysts Produced from ingesting tachyzoites

20% of cats ingesting oocysts develop a patent infection - few oocysts

Dubey 1998

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”

• Chorioretinitis, hydrocephalus, intracranial calcification

• Later in life

– 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

#’s correspond to clinical signs, please see later slides 41-43

1

2 & 3

4

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

Epidemiology

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

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/rivep/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