Phylum Apicomplexa

Lectures 38-42

For Toxoplasma gondii, what is the only host where sexual multiplication occurs?

cats (domestic and wild)

For Toxoplasma gondii, asexual replication occurs where in domsetic livestock, birds, grazing wildlife, dogs, and people?

CNS and edible tissues

The following lifecycle matches which species:

• facultative direct/indirect lifecycle

• ingestion of sporulated oocysts

• 2 sporocysts with 4 sporozoites

• ingestion of tissue cysts

Toxoplasma gondii

For Toxoplasma gondii, where does sexual reproduction occur in the cat?

small intestine

For Toxoplasma gondii, how are most cats infected?

by ingestion of tissue cysts

The eggs in this image match which species?

Toxoplasma gondii

Clinical signs of infection with Toxoplasma gondii in cats is split into what phases?

• intestinal phase

• tissue phase (asexual replication)

The following clinical signs match which phase of infection with Toxoplasma gondii in cats:

• likely behaves like other coccidia

• oocysts in stool

• diarrhea, soft stool, without specific clinical signs

intestinal phase

The following clinical signs match whcih phase of infection with Toxoplasma gondii in cats:

• respiratory disease (sneezing, light cough)

• lymphadenopathy (tachyzoites in lymph nodes, macrophages)

Tissue phase (asexual replication)

What causes the light cough in the tissue phase (asexual replication) in cats infected by Toxoplasma gondii?

intracellular replication of tachyzoites in lungs

A stray cat comes into your clinic experiencing diarrhea, sneezing, coughing, and lymphadenopathy. Organisms measuring approximately 12 micrometers like those in the image are seen on fecal examination. What is the diagnosis?

Toxoplasma gondii

What is seen in this image of lymph node aspirate?

Tachyzoites

What is seen in this image of an infected mouse brain?

Bradyzoites

What presentation of clinical disease by Toxoplasma gondii is seen for canines?

• suspect neurological disease

• lymphadenopathy

• respiratory complain

• myositis

What presentation of clinical disease by Toxoplasma gondii is seen for sheep and goat production?

abortion storms

For ewes (sheep) infected with Toxoplasma gondii, does the first exposure while pregnant protect them from abortion in subsequent pregnancies?

Yes

Livestock infected with Toxoplasma gondii are sources of what for transmission to people?

tissue cysts

How are all animals infected with Toxoplasma gondii?

ingestion of oocysts or tissue cysts

A herd of ewes has had an abortion storm in whcih 80% of animals are affected. All stages of gestation are affected, and lambs that are born are very weak. On the placentas, cotyledons have white foci of necrosis. Which one of the following choices is the primary differential diagnosis?

Toxoplasma gondii

Does Toxoplasma gondii present a zoonotic risk?

Yes

What is the primary source of all zoonotic infections for Toxoplasma gondii?

domestic and wild felidae

How do domestic and wild felidae transmit zoonotic Toxoplasma gondii?

infectious oocysts passed in feces then people and other intermediate hosts are infected by oocysts or tissue stages

What is the second leading cause of death from foodborne illness in the United States?

Toxoplasmosis

What are the effects of Toxoplasma gondii infection (Toxoplasmosis) in humans?

• congenital birth defects

• abortion to fetus when mother acquires primary infection during pregnancy

What is a major cause of mortality for HIV and other immunocompromised persons?

Toxoplasma gondii (Toxoplasmosis)

What virus can be associated with Toxoplasmic encephalitis (TE)?

Human Immunodeficiency Virus

Congenital toxoplasmosis is often asymptomatic until the second or third decade of life, when what occurs?

lesions develop in the eye

What can occur when a pregnant mother has congenital toxomplasmosis in the first trimester?

abortion or serious congenital birth defects

What can occur when a pregnant mother has congenital toxomplasmosis in the second and third trimester?

• mild retardation

• blindness

What can occur when a pregnant mother has congenital toxomplasmosis late in pregnancy?

clinically inapparent infections

What methods do we use to diagnose infection of Toxoplasma gondii?

• fecal examination

• serologic testing (IFA, ELISA, MAT)

• PCR

What specimens can we use for testing to diagnose infection of Toxoplasma gondii?

• serum

• fluids (CSF, aqueous humor, amniotic)

• tissue cysts (biopsy, necropsy)

How do we interpret serological test results for Toxoplasma gondii if the IgG result (titer) is negative (<32) and the IgM result (titer) is negative (<512)?

no serological evidence of Toxoplasma infection

How do we interpret serological test results for Toxoplasma gondii if the IgG result (titer) is negative (<32) and the IgM result (titer) is positive (>512)?

suspect early (acute) infection with Toxoplasma; obtain new specimen and test 2-3 weeks later. IgG positive test confirms suspicion

How do we interpret serological test results for Toxoplasma gondii if the IgG result (titer) is equivocal (</= 32) and the IgM result (titer) is equivocal (>/= 512)?

Subsequent re-testing fails to demonstrate measurable IgG antibody titer (>/= 32); investigate other causes for clinical symptoms

How do we interpret serological test results for Toxoplasma gondii if the IgG result (titer) is positive (>32) and the IgM result (titer) is positive (>512)?

Possible acute infection with Toxoplasma; obtain new specimen and test for rising IgG titer, 4 fold increase in IgG titer confirms suspicion

How do we interpret serological test results for Toxoplasma gondii if the IgG result (titer) is positive (>32) and the IgM result (titer) is negative or equivocal (</= 512)?

Infection with Toxoplasma for probably 1 year o longer; obtain new specimen and test for rising IgG titer; 4 fold increase in IgG titer confirms suspicion. If no change in titer assume chronic infection

Which species can potentially be associated with behavioral changes in humans and cats?

Toxoplasma gondii

Treatment of Toxoplasma gondii may or may not be indicated based on what?

• presence of active vs chronic disease

• immune status

• site of infection

• etc

What is the most important way to mitigate disease potential of Toxoplasma gondii for serologically negative pregnant women and immunocompromised patients?

prevention of exposure

Should treatment decisions for Toxoplasma gondii be based on the likelihood of cat exposure?

No, cat ownership/exposure has not been shown to increase risk of infection

What is recommended for women in regards to Toxoplasma gondii?

• women of childbearing age should be tested prior to becoming pregnant and yearly as part of annual reproductive health examination

• seronegative women should be tested regularly during prenatal examinations

• eat all meat well cooked (well done or better)

• wash all fruits and vegetables prior to consumption

• rigourous handwashing and food hygiene

• avoid gardening and other soil related activities during pregnancy

• dump cat litter boxes daily by non pregnant household member

• test household cats

Who should be contacted for up to date diagnostic and treatment protocols for Toxoplasma gondii?

CDC

When testing household cats for Toxoplasma gondii, the serologically positive or serologically negative cat is more problematic?

serologically negative

The apicoplast part of Toxoplasma gondii tachyzoite is important for what?

• important for fatty acid metabolism

• important drug target

What drugs can be used for veterinary pharmacologic management of Toxoplasma gondii?

• Trimethoprim-sulfa and Pyrimethamine

• Clindamycin

• Atovaquone

• Ponazuril/Diclazuril

Are there any curative therapies for Toxoplasma gondii?

No

Are there any FDA approved therapies for Toxoplasma gondii?

No

How do we resolve clinical disease of Toxoplasma gondii via pharmceuticals?

arresting (suppressive) rapid proliferation of the tachyzoite stage

Which drug is acknowledged as the treatment of choice for Toxoplasma gondii?

Clindamycin

Which drug is thought to act on the respiratory metabolism and inhibition of protozoa mitochondria transport and pyrimidine synthesis for Toxoplasma gondii?

Atovaquone

Which drug has activity against the apicoplast of tachyzoites of Toxoplasma gondii?

Ponazuril/Diclazuril

Which drug has rapid absorption/distribution in tissues to target activity against trachyzoites of Toxoplasma gondii?

Trimethoprim-sulfa and Pyrimethamine

What are the intermediate hosts of Toxoplasma gondii?

all endothermic vertebrates

Clinical disease of Toxoplasma gondii typically occurs in which host?

intermediate host

Recommendation for prevention of disease of Toxoplasma gondii are based on what?

hygiene and timely diagnosis

A female veterinarian is pregnant and serologically tested for toxoplasmosis. Her IgM titer is negative, but her IgG titer is positive (>64). What is the most appropriate interpretation for these results?

Both mother and baby are safe

A client visiting your practice is pregnant. She has been advised to surrender her cat because of the risk of Toxoplasmosis. What do you advise?

Clean the litterbox daily as a precaution to remove oocysts. Cook meat well, and wash fruits and vegetables.

These oocysts, measuring 10 micrometers, were found on the fecal flotation of a sneezing kitten. What is the public health significance of this finding?

The oocysts are likely Toxoplasma gondii and have zoonotic potential when sporulated

What is the only host that has sexual multiplication of Neospora caninum?

dogs (domestic and wild)

Where are oocysts of Neospora caninum in dogs?

small intestine epithelium

How does Neospora caninum differ from Toxoplasma gondii?

• immunologically

• biologically (predominately indirect lifecycle, ingestion of tissue cysts in IH)

• epidemiologically (not zoonotic, significant in cattle production)

What parasite is described by the following:

• intercellular parasite of dogs, domestic livestock, and grazing wildlife

• dogs are definitive host

• morphologically similar to T gondii

• Tachyzoites and Bradyzoites in tissues IH and DH

• Domestic livestock, grazing wildlife, and dogs are IH

Neospora caninum

How are domestic livestock, grazing wildlife, and dogs infected by Neospora caninum?

• infected by oocysts

• vertical (prenatal) transmission

• viable parasites capable of in vivo passage in IH

Which species is seen in this image?

Neospora caninum

What is the clinical significance of Neospora caninum in dogs?

• congenital infection

• asymptomatic at birth with clinical disease >3 weeks later

• posterior paresis (neuromuscular disease)

What is the clinical significance of Neospora caninum in cattle?

• reproductive disease (disease of placenta/fetus)

How do we treat infections of Neospora caninum in pet dogs?

• no FDA approved or curative treatment

• Clindamycin

• Trimethoprim sulfadiazene in combination with Pyrimethamine

How do we control and prevention infections of Neospora caninum in pet dogs?

• husbandry/mangement of risks

• do not allow access to fetal or placental tissues

• do not feed raw meat

• do not breed females previously diagnosed with clinical disease or whelped litters with affected puppies

• Avoid immunosuppressive therapies in seropositive dogs

How do we treat infections of Neospora caninum in cattle production?

• No FDA approved treatment

• Toltrazuril/ponazuril

How do we control and prevent infections of Neospora caninum in cattle production?

• restrict dog access to cattle feed and facilities

• be especially observant for signs of reproductive loss in herd

• Keep records on herd productivity

• Remove fetal/placental tissues promptly and dispose in biosecure manner

• Make effort to keep a closed herd

• Culling seropositive cows controversial

• serological assessment if outbreak suspected

Which species is seen in this image?

Sarcocystis sp

For Sarcocystis sp, where does sexual replication occur in cats and dogs?

small intestine

For Sarcocystis sp, disease is only in which host?

intermediate host

Which species is described by the following:

• obligate indirect lifecycle

• ingestion of tissur cysts in specific intermediate hosts

• dogs and cats are definitive hosts

• sporocysts with 4 sporozoites on fecal flotation

Sarcocystis sp

What are the only hosts where sexual multiplication occurs for Sarcocystis sp?

dogs and cats

True or false: In Sarcocystis sp, clinical signs are not associated with sporocyst shedding.

True

In which intermediate hosts does Sarcosystis sp display asexual replication?

domestic livestock, birds, grazing wildlife, birds

Where does asexual replication of Sarcosytis sp in intermediate hosts occur?

striated muscle or endothelial cells

Equine are accidental hosts of which Sarcocystis sp?

S. neurona

What are the natural intermediate hosts of S neurona?

opossum/various warm blooded mammals

Which species of intermediate hosts are infected by Sarcocystis sp via ingestion of tissue cysts?

sheep-dog, cow-dog, etc

How are humans infected with Zoonotic Sarcocystosis?

eating undercooked meat containing mature sarcosysts

Cattle become infected by sporocysts of Sarcosystis cruzi while grazing. These parasites then undergo how many generations of asexual replication?

two

What is the clincal significance of Sarcocystis cruzi?

• most infections are asymptomatic in dogs (definitive host)

• adverse health effects in cattle (intermediate host) including abortion, still birth, eosinophilic myositis, necrotic encephalitis, fever, anorexia, diarrhea, muscle spasm, loss of tail hair, hyperexcitablity, cachexia, weakness, decreased milk yield, calves fail to thrive or undergo rpemature death in chachectic state

How do we treat infections of Sarcocystis cruzi?

• treatment of infected hoof stock is not economically practical

• Amprolium

What is the primary etiological agent of Equine Protozoa Myloencephalitis (EPM)?

Sarcosystis neurona

What are the clinical signs of equine protozoa myloencephalitis?

neurological disease: stumbling, ataxia, incoordination, lameness, paresis, muscle atrophy, recumbency, diaphoresis, urinary incontinence, constipation

How do we diagnose equine protozoa myloencephalitis?

by serology - IgG antibodies, IFA testing to distinguish is caused by S neurona or N hughesi

In cases of Equine Protozoa Myloencephalitis, does seropositivity equate to disease?

No

How do we treat horses infected with equine protozoa myloencephalitis?

• Ponazuril

• Sulfadiazene/Pyrimethamine

How does Ponazuril work to treat EPM caused by Sarcocystis sp?

• targets mitochondria to disrupt amino acid synthesis and energy metabolism

• cross blood brain barrier into CSF

How does Sulfadiazene/Pyrimethamine work to treat EPM caused by Sarcocystis sp?

• interfere with parasite synthesis of folic acid and inhibit energy metabolism

What do we need to consider when using Sulfadiazene/Pyrimethamine to treat EPM caused by Sarcocystis sp?

• possible toxicity from long term use

• anemia, bone marrow suppression

• must replace folic acid deficiency in host with supplements

Clinical disease from neospora is primarily associated with what in dairy production?

vertical transmission from Cow to Calf

Sarcocystis neurona is a “condition” of what more than a “neurological disease” of horses?

antibody prevalence

Which coccidia spp are found in the blood?

• Hepatozoon

• Babesia

• Cytauxzoon

The following general features describe which disease:

• disease associated with infection by Haemogregarine parasites in genus Hepatozoon

• broad host range among vertebrates

• largest distrubution of species is reptiles

• disease results from asexual replication of parasite in dog intermediate host

• ticks are definitive host

Hepatozoonosis

What is the intermediate host of Haemogregarine parasites in genus Hepatozoon?

dogs

What is the definitive host of Haemogregarine parasites in genus Hepatozoon?

ticks