Etiology and Pathogenesis of Toxoplasmosis in Animals
Toxoplasma gondii is an apicomplexan protozoan that infects humans and other warm-blooded animals worldwide, including birds and marine mammals. This intracellular parasite has a facultative, indirect life cycle, reproducing sexually in enterocytes from definitive hosts and asexually in nucleated cells from intermediate hosts. Felids are the only definitive hosts of T gondii, which contaminates the environment with oocysts transmitted in feces. T gondii has three infectious stages: tachyzoites (rapidly multiplying form), bradyzoites (slow division form contained in tissue cysts), and sporozoites (in mature or sporulated oocysts). There are different T gondii genotypes, which exhibit different behaviors and virulence. Genotypes detected in South America, Africa, and Asia are considered more virulent than those predominating in Europe and North America.
T gondii is transmitted by consumption of infectious oocysts from a contaminated environment, by consumption of tissue cysts in infected meat, and by transplacental transfer of tachyzoites from mother to fetus. T gondii initiates enteroepithelial replication in unexposed felids after ingestion of uncooked tissues containing cysts. Bradyzoites are released from tissue cysts by digestion in the stomach and small intestine, invading intestinal epithelium, and undergoing asexual and sexual replication, culminating in the release of oocysts (~10 mcm in diameter) in the feces. Oocysts are first evident in the feces 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 they shed oocysts only once in their lifetime; however, immunocompromised animals can re-shed oocysts. Felids are also intermediate hosts for extraintestinal asexual multiplication of the parasite, especially in nervous system cells. Neurologic and ocular lesions can arise in immunocompromised and elderly cats.
After being consumed in uncooked meat containing tissue cysts (carnivores) or in 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 and other tissues. After asexual 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 are banana shaped and measure 4–6 × 2–3 mcm. Susceptible species, and young, immunocompromised animals (e.g., puppies, kittens, piglets) may die from generalized toxoplasmosis at this stage of illness. Adult animals mount a powerful, cell-mediated immune response (mediated by cytokines) and control infection, driving the tachyzoites into the tissue cyst or bradyzoite stage. Tissue cysts usually occur in neurons; however, they also occur in other tissues, such as muscles. Individual cysts are microscopic, up to 100 mcm 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; thus serving as an important source of infection for scavengers, both carnivores, and omnivores.
Clinical Findings of Toxoplasmosis in Animals
The tachyzoite is the stage responsible for tissue damage in toxoplasmosis; therefore, clinical signs depend on the affected tissue, the number of tachyzoites released, and the ability of the host immune system to limit replication and transmission. Because adult immunocompetent animals control tachyzoite transmission efficiently, toxoplasmosis is usually a subclinical illness. However, in susceptible species, as well as in young and immunocompromised animals (particularly puppies, kittens, and piglets), tachyzoites are transmitted 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, goats, cervids, and sometimes pigs. After infection of a pregnant ewe, tachyzoites are transmitted via the bloodstream to placental cotyledons, causing necrosis. Tachyzoites may also be transmitted 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, mainly expressed as neurologic and respiratory disorders.
Women who acquire T gondii during pregnancy can develop a fever, and transplacental passage of tachyzoites to the fetus may occur. Veterinarians have a key role in preventing this zoonotic disease by recognizing contamination of the environment and water by oocysts, by observing the presence of cysts in animal tissues, and by helping to develop, disseminate, and apply control measures.
Diagnosis of Toxoplasmosis in Animals
Indirect diagnosis by serologic testing
Postmortem diagnosis via histologic, bioassay, and molecular methods
Toxoplasmosis is diagnosed by biologic, serologic, or histologic methods; or some combination of these. Clinical signs of toxoplasmosis are nonspecific and are not sufficiently characteristic for a definitive diagnosis. Antemortem diagnosis may be accomplished by indirect hemagglutination assay, indirect fluorescent antibody assay, latex agglutination test, or ELISA testing. IgM antibodies appear sooner after infection than IgG antibodies; generally, however, IgM antibodies do not persist past 3 months 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 serum samples obtained during the acute and convalescent stages (3–4 weeks apart) and must show at least a fourfold increase/decrease in titer (seroconversion). In addition, CSF and aqueous humor samples may be analyzed for the presence of tachyzoites or anti–T gondii antibodies.
Postmortem, tachyzoites may be evident in tissue impression smears. Also histologic examination of tissue sections may reveal the presence of tachyzoites or bradyzoites, which could be specifically marked by immunohistochemical staining. T gondii is morphologically similar to other protozoal parasites and must be differentiated from Sarcocystis species and Neospora caninum, which may also be involved in abortions and infection of neurologic tissues. Application of specific PCR assays allows diagnosis from tissue DNA samples. Once the presence of parasitic DNA is confirmed, the sample can be further processed for parasite genotyping.
Treatment of Toxoplasmosis in Animals
For acute toxoplasmosis: anti-coccidial drugs, administered as soon as possible after infection is suspected
For primary infection: specific treatment to avoid or minimize vertical transmission
For animals other than humans, treatment of toxoplasmosis is seldom warranted. Sulfadiazine (15–25 mg/kg, PO, every 12 hours for 4 weeks) and pyrimethamine (0.44 mg/kg, PO, every 12 hours for 4 weeks) act synergistically and are widely administered for treatment of toxoplasmosis. Trimethoprim-sulfamethoxazole (15 mg/kg, PO, every 12 hours for 4 weeks) is also widely recommended in dogs and cats. Although 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. Other drugs, including diaminodiphenylsulfone, atovaquone, and spiramycin, may also be administered to treat toxoplasmosis in difficult cases. For dogs and cats, clindamycin is the treatment of choice, administered PO every 12 hours for 3–4 weeks at 10–12.5 mg/kg in dogs and 25–50 mg/kg in cats. Toltrazuril, ponazuril, and diclazuril may be administered to treat acute toxoplasmosis, as well as to reduce the shedding of oocysts by cats. No drugs are particularly effective at the bradyzoite stage.
Prevention and Zoonotic Risk of Toxoplasmosis in Animals
Toxoplasmosis is an important zoonotic disease. In some areas of the world, as much as 60% of the human population has serum IgG titers for T gondii and is likely to be persistently infected. Toxoplasmosis is a major concern for people with compromised immune systems. 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 (reactivation) rather than from primary infection. Toxoplasmosis is also a concern for pregnant women because tachyzoites can migrate transplacentally and cause neurologic disorders in the fetus. Infection with T gondii may occur after ingestion of undercooked meat or accidental ingestion of oocysts from cat feces thorough contaminated water or vegetables.
To prevent infection, hands should be washed thoroughly with soap and water after contact with meat or potentially contaminated environments. The stages of T gondii are killed by cooking and contact with boiling water, and boiling water should be used to clean all cutting boards, sink tops, knives, and other materials. T gondii can also be killed by freezing. Tissue cysts are killed by heating throughout to 67°C (152.6°F) or by cooling to −13°C (8.6°F). Toxoplasma individuals in tissue cysts are also killed by exposure to 0.5 kilorad of gamma irradiation. Meat of any animal should be cooked to 67°C (152.6°F) 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.
There is currently no vaccine to prevent toxoplasmosis in humans. Some countries have approved a vaccine to prevent abortions in sheep.
Toxoplasmosis is a zoonosis that affects all warm-blooded animals worldwide.
A high proportion of animals and humans are infected without clinical signs. Different T gondii genotypes could generate different clinical outcomes.
Immunocompromised individuals may develop generalized toxoplasmosis with multiorgan failure.
T gondii may be transmitted vertically and produce fetal lesions and abortions.
For More Information
Dubey JP. Toxoplasmosis of Animals and Humans. Second Edition. CRC Press; 2010.
ToxoDB: Toxoplasma Informatics Resources
OIE Terrestrial Manual 2017, Chapter 2.9.9: Toxoplasmosis
Moré G, Venturini MC, Pardini LL, Unzaga JM. Toxoplasma. In: Florin-Christensen M, Schnittger L, eds. Parasitic Protozoa of Farm Animals and Pets. Springer; 2018:149-168.
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