Toxoplasma gondii is a protozoan parasite that infects humans and other warm-blooded animals, including birds and marine mammals (see Marine Mammals: Toxoplasmosis). It has been found worldwide from Alaska to Australia.
Etiology and Pathogenesis
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 µm 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.
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.
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).
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.
Prevention and Zoonotic Risk
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. 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 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.
Last full review/revision March 2012 by J. P. Dubey, MVSc, PhD