Toxoplasma gondii (T. gondii) is a tissue protozoan with worldwide distribution and an exceptionally wide host range. Virtually all warm blooded animals can become infected. Domestic cats and wild felids are the only known definitive hosts producing and excreting infectious oocysts in their faeces, but cats can also act as intermediate hosts and suffer from a wide range of clinical signs.  All other susceptible species, including food animals and humans, act as intermediate hosts exclusively.

Cats are one potential source of T. gondii infection for humans and it is therefore important for veterinarians to understand the biology of the organism in order to be able to advise cat owners regarding the potential zoonotic risk and to ensure that no cats are euthanized needlessly. More detailed information on T. gondii as a zoonosis see The Cat Group policy statement 6.

There are three infectious stages of T. gondii and cats and humans can become infected with the organism by one of three major modes of transmission:

Following infection of a cat with T. gondii, the infectious organism completes two different life cycles. The enteroepithelial life cycle takes place in the epithelial cells of the small intestine and leads to the development of oocysts which are excreted in the faeces and become infectious after exposure to air and humidity within 1 to 5 days. In most cats that ingest bradyzoits in tissue cysts the parasite will complete the enteroepithelial life cycle and these cats will shed oocysts about ten days later. However only 20% of cats being infected with oocysts will go on to produce and shed oocysts. Cats can shed large numbers of oocysts in their faeces for usually less than 2 weeks after first exposure to the parasite. Cats rarely re-shed occysts after the first exposure. 

The extraintestinal life cycle takes place regardless of which infectious stage of T. gondii infects the cat. During the extraintestinal life cycle which occurs simultaneously to the enteroepithelial cycle the infectious organisms penetrate through the small intestinal wall and replicate in different tissues (organs) throughout the body. The rapidly replicating forms of T. gondii are termed tachyzoites. This life cycle ultimately results in formation of tissue cysts which contain slowly replicating organisms (bradyzoites). This is the only life cycle found in all intermediate hosts. 

Most cats with access to the outdoors are thought to become infected by eating infected intermediate hosts such as small rodents and birds harbouring toxoplasma tissue cysts. Cats can however also become infected if they are fed raw or undercooked meat containing tissue cysts. In rare cases kittens can become infected transplacentally or lactationally through tachyzoites circulating in the queen’s blood during parasitaemia. After infection of both humans and cats it is considered likely that the infection persists in tissues lifelong.

Clinical toxoplasmosis
Clinical disease in cats (and other species) is rare with T. gondii infection. It is not fully understood why some cats will go on to develop significant illness whereas others remain asymptomatic. Factors such as age of the host, strain of T. gondii, number of organisms and stage of the parasite ingested may all play a role. Also stress and concurrent immunosuppression may make an individual more susceptible to infection.

Clinical signs can develop either following primary infection or as a result of reactivation of bradyzoites from tissue cysts. The clinical signs seen with T. gondii infection depend on the organs affected and the degree of tissue damage caused. All cell types appear susceptible and intracellular growth of tachyzoites results in cell necrosis.

Self-limiting small intestinal diarrhoea can be seen in cats that ingest tissue cysts for the first time. This is considered to be a result of the parasite replicating in the intestinal wall. The clinical signs of extraintestinal toxoplasmosis are numerous and include persistent or intermittent fever, weight loss, anorexia, muscle pain, stiffness of gait and shifting leg lameness. Lethargy and dyspnoea as a result of pulmonary toxoplasmosis are commonly recognized. Cats with hepatic toxoplasmosis develop hepatitis or cholangiohepatits and show icterus. Further clinical signs are vomiting, diarrhoea, abdominal effusion, neurologic deficits and dermatitis. Cases of ocular toxoplasmosis are common and can occur without other systemic manifestations. These cats show signs of anterior or posterior uveitis such as aqueous flare, keratic precipitates and chorioretinitis. As a result lens luxation with secondary glaucoma can follow. Neurological signs such as seizures or neurological deficits can develop following CNS infection. Sudden death can also be seen. Common sites with evidence of toxoplasma infection on post mortem examination in one study of 100 cats were the lungs, brain, liver, heart, pancreas, eyes and adrenal glands.

The clinical signs can develop rapidly and lead to the death of the cat within just one day or have a much slower non-fatal course. 

The clinical signs associated with toxoplasmosis are most severe in transplacentally or lactationally infected kittens where tachyzoite replication can be overwhelming and can result in death. Infected kittens can be stillborn or die before weaning. The clinical signs are often related to infection of the liver, lungs and CNS. Non-specific signs such as lethargy, anorexia, hypothermia and vocalisation are also commonly seen. Chorioretinitis with or without concurrent uveitis can be the only clinical signs in transplacentally infected kittens.

Diagnosis
The diagnosis of T. gondii infection can be very challenging. Since T. gondii can affect a variety of organs, often simultaneously, numerous clinicopathological and radiographic or ultrasonographic changes can be seen, however none of them are pathognomic. The changes seen often reflect the disease of the organ systems affected. Radiographs of the thorax can show an interstitial or alveolar lung pattern and in rare cases pleural effusion.  Abdominal radiographic findings can include evidence of hepatomegaly, peritoneal effusion and loss of serosal detail in the right cranial quadrant suggestive of pancreatitis.

Non-specific haematological changes such as non-regenerative anaemia, neutrophilia, lymphocytosis, monocytosis and eosinophilia can be seen. Severely affected cats can show neutropenia and lymphopenia. Amongst other changes serum biochemistry can reveal elevations in ALT, AP and creatine kinase activity and hyperbilirubinaemia and hypoalbuminaemia can be present. In chronic cases hyperglobulinaemia has been described.

In rare cases histopathology or cytology can lead to a definitive ante mortem diagnosis by demonstrating bradyzoites in tissue samples or tachyzoites in body fluids such as blood, cerebrospinal fluid (CSF), bronchoalveolar fluid (BALF), peritoneal and thoracic effusions or aqueous humor.

Several laboratories in the USA offer polymerase chain reaction (PCR) testing for T. gondii. PCR can detect the parasite’s DNA in tissue and body fluids and is regarded as more sensitive and specific than cytology and histopathology. T. gondii DNA can however be found in blood from healthy cats. Therefore, a positive PCR result does not always correlate with clinical disease.

Analysis of CSF from cases with suspected toxoplasmosis can show normal or elevated protein levels and nucleated cell counts of up to 28 cells/ml can be seen with lymphocytes predominating.  Testing for T. gondii specific antibodies and DNA in CNS or aqueous humor is considered the most accurate way of diagnosing CNS and ocular toxoplasmosis. However the locally produced antibodies must be differentiated from those that passively diffused through the damaged vascular barrier.

Examination of faecal samples for the presence of T. gondii oocysts is difficult and usually not useful since clinical signs normally do not develop until after oocyst shedding has stopped. T. gondii oocysts cannot be distinguished morphologically from oocysts of the coccidian Hamondia and Besnoitia.

Performing serological tests does not provide a definitive diagnosis of clinical disease related to T. gondii, but it can be useful. Antibodies of the IgM class can be detected as early as 2 to 4 weeks following infection, however by 16 weeks the titre has usually returned to zero. Therefore a positive IgM titre correlates best with clinical toxoplasmosis. Cats with ocular toxoplasmosis and FIV co-infection can have persistently positive IgM titres. Seroconversion for IgG occurs within 2 to 3 weeks of infection and the IgG titre remains high for years. The maximum IgG titre is usually reached within 2-3 weeks. Demonstration of an at least four fold increase in the IgG titre also suggests active infection.  It may however be possible that by the time diagnostic tests are performed a cat has already reached its maximum IgG titre and the IgM titre has returned to zero which complicates diagnosis.

Negative antibody titres in serum, CSF and aqueous humor would suggest that toxoplasmosis can be ruled out. A combination of the following findings increases the index of suspicion of active toxoplasmosis:

Treatment
Clindamycin (10-12 mg/kg PO q 12 h) or trimethoprim-sulfonamide combinations (15 mg/kg PO q 12 h) are commonly used for the treatment of toxoplasmosis. Both drugs are used for at least 4 weeks and can be used in combination. Trimethoprim-sulfonamide might be the drug of choice in CNS toxoplasmosis since it penetrates an intact blood-brain barrier better than clindamycin. The combination of pyrimethamine and a sulphonamide drug can also be used in the treatment of toxoplasmosis. However both trimethoprim and pyrimethamine alone and in combination with a sulphonamide drug can results in bone marrow suppression and sulphonamides can cause kidney disease. Therefore haematology and serum biochemistry profiles should be monitored regularly. Supplementation with folic acid (5 mg/day) can be used to prevent or correct bone marrow suppression. 

Cats suffering from systemic as well as ocular toxoplasmosis should also receive topical, oral or parenteral corticosteroids in order to prevent lens luxation and glaucoma secondary to uveitis. In cases of isolated ocular toxoplasmosis topical corticosteroids might be sufficient unless the uveitis is chronic or recurrent.

Clinical doses of corticosteroids do not appear to be associated with recrudescence of latent disease; however immunosuppressive treatment with cyclosporin has been associated with dissemination. Therefore, it might be beneficial to test all cats for evidence of T. gondii infection prior to treating them with cyclosporin and to pre-treat seropositive cats with anti-T. gondii medications.

Prognosis
Replication of the parasite within the liver or lungs usually results in a poor prognosis, especially in immunosuppressed cats. Most clinical signs caused by toxoplasmosis resolve within 2 to 3 days of treatment. If an improvement in fever and muscle hyperaesthesia is not seen within 3 days and toxoplasmosis is still the main differential diagnosis, a different anti-Toxoplasma drug should be used. Clinical signs related to CNS and ocular toxoplasmosis take longer to respond to therapy. Cats concurrently infected with FIV respond less well to therapy.