Pathogenesis: Many host species exhibit an age-related resistance to disease therefore most infections in adults and weaned individuals are asymptomatic. In susceptible hosts, symptomatic infections may be acute, subacute or chronic. Acute infections by proliferating tachyzoites cause flu-like symptoms, including lymphadenitis, fever, headache, muscle pain and anaemia. Symptoms generally subside with the development of immunity, but may sometimes persist producing subacute disease, characterized by extensive lesions in the lung, liver, heart, brain or eyes. Postnatal infections often involve lymphadenitis, myocarditis, central nervous system involvement and retinochoroiditis. Chronic infections by encysted bradyzoites usually cause few clinical signs, although degenerating cysts have been associated with hypersensitive inflammatory reactions, resulting in, for example, encephalitis, myocarditis and/or chorioretinitis. The tissue cysts lay quiescent (dormant) in the tissues for some time, occupying little space and apparently causing few functional deficits, although there is contradictory evidence that infections may be associated with some learning disabilities, slower reflexes and altered behaviour in intermediate hosts. Latent cyst infections may be reactivated in immunocompromised patients (i.e. those undergoing immunosuppressive therapy or with acquired immunodeficiencies) resulting in cell lysis, expanding focal lesions, rapid dissemination, encephalopathy and meningoencephalitis. Infections may also be transmitted transplacentally. If the mother/dam contracts infection during pregnancy, parasites may cross the placenta and infect the foetus causing spontaneous abortion, stillbirth or congenital abnormalities, such as hydrocephalus, brain calcification, chorioretinitis and mental retardation. Nonetheless, if the mother/dam is infected prior to pregnancy, her immunity is transferred to her foetus which is consequently protected. Infections in cats by enteric sexual developmental stages are generally subclinical, transient and leave the cat with a solid protective immunity against subsequent oocyst production.

Mode of transmission: Infections are transmitted horizontally between hosts by the ingestion of oocysts excreted by cats, and vertically between mother and offspring by transplacental or even transmammary transmission of proliferative tachyzoites. Infections may also be transferred between intermediate hosts through the food chain via carnivorism, the ingestion of fresh or undercooked meat containing viable cysts. Bradyzoites released during digestive processes are resistant to enzymatic digestion and revert back to tachyzoite stages which infect the host, multiply, spread and lead to new cyst formation. Infections are more prevalent in human populations which have traditional cultural practices involving the consumption of raw or partially cooked meat (e.g. steak tartare, partly cured smallgoods). Oocysts excreted by cats take 1-5 days to sporulate before they become infective and they are resistant to external environmental conditions and may remain viable in contaminated soil and water for some time.

Differential diagnosis: Parasites may be detected in autopsy or biopsy material by histology, immunolabelling or in vivo culture following inoculation into laboratory rodents. Zoites in smears stain well with Giemsa and other Romanowsky stains while cysts in sections have silver-positive walls and the bradyzoites are strongly PAS (periodic acid-Schiff) positive. Monoclonal and polyclonal antibody labels have also been used to detect parasites in tissue sections, and molecular studies using polymerase chain reaction (PCR) amplification techniques have detected parasite DNA in host tissues. Most infections, however, are diagnosed serologically and a range of immunoassays (fluorescence, agglutination and enzyme-based) are commercially available. Recent/acute infection is indicated by a 4-16 fold increase in specific antibody titre over a two-week period, or by the detection of specific IgM antibody titres.

Treatment and control: Chemotherapy is successful when pyrimethamine and sulphonamides are given together as they act synergistically. The toxic side-effects of bone marrow depression can be relieved by the administration of folinic acid. Clindamycin and spiramycin have also been reported to be effective. The risk of transmission can be reduced by maintaining high standards of hygiene (particularly where cats are involved), by thoroughly cooking or deep-freezing meat prior to consumption and washing potentially contaminated foodstuffs. Molecular vaccines are currently being developed for high risk patient groups, and a live vaccine using a low-virulent non-persistent strain has been marketed to protect sheep against toxoplasmosis.

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