Toxoplasma gondii

Toxoplasma gondii is a species of parasitic protozoa in the genus Toxoplasma. The definitive host of T. gondii is the cat, but the parasite can be carried by many warm-blooded animals (birds or mammals, including humans). Toxoplasmosis, the disease of which T. gondii is the causative agent, is usually minor and self-limiting but can have serious or even fatal effects on a fetus whose mother first contracts the disease during pregnancy or on an immunocompromised human or cat.

Life cycle
The life cycle of T. gondii has two phases. The sexual part of the life cycle (coccidia like) takes place only in cats, both domestic and wild (family Felidae), which makes cats the parasite's primary host. The second phase, the asexual part of the life cycle, can take place in other warm-blooded animals, including cats, mice, humans, and birds. The hosts in which asexual reproduction takes place is called the intermediate host. Rodents are the typical intermediate host.

In both kinds of hosts, the Toxoplasma parasite invades cells and forms a space called a vacuole. Inside this specialized vacuole, called a parasitophorous vacuole, the parasite forms bradyzoites, which are the slowly replicating versions of the parasite. The vacuoles containing the reproductive bradyzoites form cysts mainly in the tissues of the muscles and brain. Since the parasites are inside cells, they are safe from the host's immune system, which does not respond to the cysts.

Toxoplasma's resistance to antibiotics varies, but the cysts are very difficult to eradicate entirely. Inside the vacuoles, T. gondii replicates itself (by endodyogeny) until the infected cell fills with parasites and bursts, releasing tachyzoites, the motile, asexually reproducing form of the parasite. Unlike the bradyzoites, the free tachyzoites are usually efficiently cleared by the host's immune system, although some of them manage to infect cells and form bradyzoites, thus maintaining the infection.

Tissue cysts are ingested by a cat (e.g., by feeding on an infected mouse). The cysts survive passage through the stomach of the cat and the parasites infect epithelium of the small intestine where they undergo sexual reproduction and oocyst formation. Oocysts are shed with the feces. Animals and humans that ingest oocysts (e.g., by eating unwashed vegetables) or tissue cysts in improperly cooked meat become infected. The parasite enters macrophages in the intestinal lining and is distributed via the blood stream throughout the body.

Similar to the mechanism used in many viruses, Toxoplasma is able to dysregulate host’s cell cycle by holding cell division before mitosis (the G2/M border). This dysregulation of the host’s cell cycle is caused by a heat-sensitive secretion (with a molecular mass larger than 10 kDa). Infected cells secrete the factor which inhibits the cell cycle of neighboring cells. The reason for Toxoplasma’s dysregulation is unknown, but studies have shown that infection is preferential to host cells in the S-phase and host cell structures with which Toxoplasma interacts may not be accessible during other stages of the cell cycle.

Acute stage Toxoplasma infections can be asymptomatic, but often give flu-like symptoms in the early acute stages, and like flu can become, in very rare cases, fatal. The acute stage fades in a few days to months, leading to the latent stage. Latent infection is normally asymptomatic; however, in the case of immunocompromised patients (such as those infected with HIV or transplant recipients on immunosuppressive therapy), toxoplasmosis can develop. The most notable manifestation of toxoplasmosis in immunocompromised patients is toxoplasmic encephalitis, which can be deadly. If infection with T. gondii occurs for the first time during pregnancy, the parasite can cross the placenta, possibly leading to hydrocephalus or microcephaly, intracranial calcification, and chorioretinitis, with the possibility of spontaneous abortion (miscarriage) or intrauterine death.

Toxoplasmosis
T. gondii infections have the ability to change the behavior of rats and mice, making them drawn to, rather than fearful of, the scent of cats. This effect is advantageous to the parasite, which will be able to sexually reproduce if its host is eaten by a cat. The infection is highly precise, as it does not affect a rat's other fears such as the fear of open spaces or of unfamiliar-smelling food.

Studies have also shown behavioral changes in humans, including slower reaction times and a sixfold increased risk of traffic accidents among infected males, as well as links to schizophrenia including hallucinations and reckless behavior. Recent epidemiologic studies by Stanley Medical Research Institute and Johns Hopkins University Medical Center indicate that infectious agents may contribute to some cases of schizophrenia. A study of 191 young women in 1999 reported higher intelligence and lower guilt proneness in Toxoplasma-positive subjects.

The prevalence of human infection by Toxoplasma varies greatly between countries. Factors that influence infection rates include diet (prevalence is possibly higher where there is a preference for less-cooked meat) and proximity to cats.

History
The organism was first described in 1908 in Tunis by Charles Nicolle and Louis Manceaux within the tissues of the gundi (Ctenodactylus gundi). In the same year it was also described in Brazil by Alfonso Splendore in rabbits.