Toxoplasmosis - Cat and Dog

Description

Toxoplasma gondii is an obligate, intracellular coccidian parasite that is capable of infecting most mammals including man. Cats and other Felidae are the definitive host for T. gondii, and all other mammals are intermediate hosts. Toxoplasma gondii has three infectious stages: 1) sporozoites contained in oocyts; 2) an actively reproducing stage called tachyzoites; and 3) slowly multiplying bradyzoites. This means that the protozoa can be transmitted by ingestion of oocyst-contaminated food or water, or by consumption of infected tissue. Transplacental infection is also possible.

Enteroepithelial Life Cycle This cycle is found only in the definitive feline host. Most cats are thought to become infected by ingesting intermediate hosts infected with tissue cysts. Bradyzoites are released in the stomach and intestine from the tissue cysts when the cyst wall is dissolved by digestive enzymes. Bradyzoites penetrate the epithelial cells of small intestine and give rise to schizonts initiate the five types (ABE) of predetermined asexual stages and merozoites released from schizonts form male and female gamonts. After fertilization a wall is formed around the fertilized macrogamont to form an oocyst. Oocysts are round to oval, 10 � 12 �m, and are unsporulated (uninfective) when passed in feces. After exposure to air and moisture for 1 to 5 days, oocysts sporulate and contain two sporocysts, each with four sporozoites. The entire enteroepithelial (coccidian) cycle of T. gondii can be completed within 3 to 10 days after ingestion of tissue cysts and occurs in up to 97% of naive cats. However, after ingestion of oocysts or tachyzoites, the formation of oocysts is delayed until 18 days or more, and only 20% of cats fed oocysts will develop patency. Felids are the only definitive hosts of T gondii ; both wild and domestic cats therefore serve as the main reservoir of infection. There are 3 infectious stages of T gondii ; tachyzoites (rapidly multiplying form), bradyzoites (tissue cyst form), and sporozoites (in oocysts). T gondii is transmitted by consumption of infectious oocysts in cat feces, consumption of tissue cysts in infected meat, and by transplacental transfer of tachyzoites from mother to fetus. T gondii initiates enteroepithelial replication in unexposed cats after ingestion of uncooked meat containing tissue cysts. Bradyzoites are released from tissue cysts by digestion in the stomach and small intestine, invade intestinal epithelium, and undergo sexual replication, culminating in the release of oocysts (10 µm diameter) in the feces. Oocysts are first seen in the feces at 3 days after infection and may be released for up to 20 days. Oocysts sporulate (become infectious) outside the cat within 1-5 days, depending on aeration and temperature, and remain viable in the environment for several months. Cats generally develop immunity to T gondii after the initial infection and therefore shed oocysts only once in their lifetime. Following consumption of uncooked meat containing tissue cysts (carnivores) or feed or drink contaminated with cat feces containing oocysts (all warm-blooded animals), T gondii initiates extraintestinal replication. Bradyzoites and sporozoites, respectively, are released and infect intestinal epithelium. After several rounds of epithelial replication, tachyzoites emerge and disseminate via the bloodstream and lymph. Tachyzoites infect tissues throughout the body and replicate intracellularly until the cells burst, causing tissue necrosis. Tachyzoites measure 4-6 × 2-4 µm in diameter and stain with Giemsa. Young and immunocompromised animals may succumb to generalized toxoplasmosis at this stage. Older animals mount a powerful cell-mediated immune response to the tachyzoites (mediated by cytokines) and control infection, driving the tachyzoites into the tissue cyst or bradyzoite stage. Tissue cysts are usually seen in neurons but also occur in other tissues. Individual cysts are microscopic, up to 70 m in diameter, and may enclose hundreds of bradyzoites in a thin, resilient cyst wall. Tissue cysts in the host remain viable for many years, and possibly for the life of the host.

Diagnosis

Clinical Signs

The tachyzoite is the stage responsible for tissue damage; therefore, clinical signs depend on the number of tachyzoites released, the ability of the host immune system to limit tachyzoite spread, and the organs damaged by the tachyzoites. Because adult immunocompetent animals control tachyzoite spread efficiently, toxoplasmosis is usually a subclinical illness. However, in young animals, particularly puppies, kittens, and piglets, tachyzoites spread systemically and cause interstitial pneumonia, myocarditis, hepatic necrosis, meningoencephalomyelitis, chorioretinitis, lymphadenopathy, and myositis. The corresponding clinical signs include fever, diarrhea, cough, dyspnea, icterus, seizures, and death. T gondii is also an important cause of abortion and stillbirth in sheep and goats and sometimes in pigs. After infection of a pregnant ewe, tachyzoites spread via the bloodstream to placental cotyledons, causing necrosis. Tachyzoites may also spread to the fetus, causing necrosis in multiple organs. Finally, immunocompromised adult animals (eg, cats infected with feline immunodeficiency virus) are extremely susceptible to developing acute generalized toxoplasmosis.

Laboratory Tests

• Serology
  • Sabin-Feldman Dye test (old method)
  • ELISA
  • Mouse inoculation for confirmation
  • 30-80% test seropositive
  • Each cat sheds oocysts for 1-2 weeks of its life

Diagnosis is made by biologic, serologic, or histologic methods, or by some combination of the above. Clinical signs of toxoplasmosis are nonspecific and are not sufficiently characteristic for a definite diagnosis. Antemortem diagnosis may be accomplished by indirect hemagglutination assay, indirect fluorescent antibody assay, latex agglutination test, or ELISA. IgM antibodies appear sooner after infection than IgG antibodies but generally do not persist past 3 mo after infection. Increased IgM titers (>1:256) are consistent with recent infection. In contrast, IgG antibodies appear by the fourth week after infection and may remain increased for years during subclinical infection. To be useful, IgG titers must be measured in paired sera from the acute and convalescent stages (3-4 wk apart) and must show at least a 4-fold increase in titer. Additionally, CSF and aqueous humor may be analyzed for the presence of tachyzoites or anti- T gondii antibodies. Postmortem, tachyzoites may be seen in tissue impression smears. Additionally, microscopic examination of tissue sections may reveal the presence of tachyzoites or bradyzoites. T gondii is morphologically similar to other protozoan parasites and must be differentiated from Sarcocystis spp (in cattle), S neurona (in horses), and Neospora caninum (in dogs).

Treatment

Prevention

• Cat
  • Impossible if cat is allowed outdoors due to hunting
  • If kept indoors, only canned food should be fed and vermin controlled
  • ELISA to check if seropositive

For animals other than humans, treatment is seldom warranted. Sulfadiazine (15-25 mg/kg) and pyrimethamine (0.44 mg/kg) act synergistically and are widely used for treatment of toxoplasmosis. While these drugs are beneficial if given in the acute stage of the disease when there is active multiplication of the parasite, they will not usually eradicate infection. These drugs are believed to have little effect on the bradyzoite stage. Certain other drugs, including diaminodiphenylsulfone, atovaquone, and spiramycin are also used to treat toxoplasmosis in difficult cases. Clindamycin is the treatment of choice for dogs and cats, at 10-40 mg/kg and 25-50 mg/kg respectively, for 14-21 days.

Zoonosis

T  gondii  is an important zoonotic agent. In some areas of the world, up to 60% of the human population have serum IgG titers to T  gondii  and are likely to be persistently infected. Toxoplasmosis is a major concern for people with immune system dysfunction (eg, people infected with human immunodeficiency virus). In these individuals, toxoplasmosis usually presents as meningoencephalitis and results from the emergence of T  gondii  from tissue cysts located in the brain as immunity wanes rather than from primary T  gondii  infection. Toxoplasmosis is also a major concern for pregnant women because tachyzoites can migrate transplacentally and cause birth defects in human fetuses. Infection of women with T  gondii  may occur after ingestion of undercooked meat or accidental ingestion of oocysts from cat feces. To prevent infection, the hands of people handling meat should be washed thoroughly with soap and water after contact, as should all cutting boards, sink tops, knives, and other materials. The stages of T  gondii  in meat are killed by contact with soap and water. T  gondii  organisms in meat can also be killed by exposure to extreme cold or heat. Tissue cysts in meat are killed by heating the meat throughout to 67°C or by cooling to -13°C. Toxoplasma  in tissue cysts are also killed by exposure to 0.5 kilorads of gamma irradiation. Meat of any animal should be cooked to 67°C before consumption, and tasting meat while cooking or while seasoning should be avoided. Pregnant women should avoid contact with cat litter, soil, and raw meat. Pet cats should be fed only dry, canned, or cooked food. The cat litter box should be emptied daily, preferably not by a pregnant woman. Gloves should be worn while gardening. Vegetables should be washed thoroughly before eating because they may have been contaminated with cat feces.

At present there is no vaccine to prevent toxoplasmosis in humans.

Links

• Cornell College of Veterinary Medicine Toxoplasmosis Factsheet
• Feline Advisory Bureau: Toxoplasmosis in cats and man
• The Merck Veterinary Manual - Toxoplasmosis

dogs

• Caused by Toxoplasma gondii
• Cats are definitive hosts but other species may become intermediate hosts if they ingest the oocysts
• Usually induces antibody response but remains silent clinically
• Often show clinical signs when immunosuppressed
• Involves many different tissues
• Multifocal necrotising interstitial pneumonia
• Proliferation of type II pneumocytes
• Macrophage and neutrophil infiltration