Posted by: Viktor Mar | 2013 January 19

Another reason to dislike domestic cats

Even though most of this is known, the suicidal part is new to me.

Toxoplasma gondii is a species of parasitic protozoa in the genus Toxoplasma.[1]

The definitive host of T. gondii is the cat, but the parasite can be carried by many warm-blooded animals (birds[2] 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. Around a third of people worldwide carry the parasite, with most catching it by consuming undercooked meat, especially lamb, pork and venison or by ingesting water, soil or anything contaminated by feline feces.

According to Merck the standard drug to counter infection is pyrimethamine, but most immunocompetent asymptomatic people infected with T. gondii, with the exception of neonates and pregnant women, require no treatment[3] though recent studies have indicated an influence of T. gondii on suicidal behaviours in humans [4] which — if widely confirmed — might warrant treatment attention. However, drugs are only effective during active infection (tachyzoite stage); there is currently no way to treat latent infections (bradyzoite stage) so a host once infected is infected for life. This is problematic when previously immunocompetent hosts become immunocompromised (for example in the case of cancer or AIDS), allowing reactivation of the infection.

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),[5] 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.[5]

Life cycle of T. gondii (N.B. tachyzoites cannot invade red blood cells, as they are not nucleated).

T. gondii constructing daughter scaffolds within the mother cell.

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.[6] The vacuoles containing the reproductive bradyzoites form cysts mainly in the tissues of the muscles and brain.

Toxoplasma’s resistance to anti-toxoplasmosis medication 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.[citation needed]

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.[citation needed]

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).[7] This dysregulation of the host’s cell cycle is caused by a heat-sensitive secretion (with a molecular mass larger than 10 kDa).[8] 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.[9][10][11][12][13]

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, during an activity such as changing cat litter of a cat infected with T. gondii (uptake of cyst by inhalation, followed by ingestion as the mucus is cleared), 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.[citation needed]

An in vitro study showed that ivermectin significantly inhibited T. gondii replication.[14][15]


Main article: Toxoplasmosis

Diagram of Toxoplasma gondii structure

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.[16] The infection is widespread in the brain, with more cysts targeting the parts of the brain corresponding to fear. The widespread nature of the infection causes many previously unnoticed symptoms in the rats.[17]


This parasite can be diagnosed typically by serologic tests. They do this by detecting immunoglobulin antibodies that appear within several weeks of infection. Living parasites can be also found in the sample (blood, cerebrospinal or other body fluids) but the process is more difficult and thus not usually used. Direct observation of the parasite is possible in cerebrospinal fluid (CSF), stained tissue sections or other biopsy samples but these techniques are used less frequently due to their difficulty.[18]

Human epidemiology

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.[19]

The rates of positive sero-prevalence in women at child-bearing age between 1990 and 2000 were 58% in Central European countries, 51–72% in several Latin-American countries and 54–77% in West African countries. Low seroprevalence, 4–39%, was reported in southwest Asia, China and Korea as well as in cold climate areas such as Scandinavian countries (11–28%).[20] Although T. gondii infection is thought to be detrimental it may have positive effects on some individuals, contrary to the mainstream view. For example T. gondii seems to stop brain deterioration to Alzheimer’s disease.[21] T. gondii has also been linked to pre-natal depression, as well as increased anxiety and depression during pregnancies. It has also been linked with mood disturbances in nonpregnant populations,[22] including schizophrenia and suicidal behavior.[23]

Effects on human patients


Toxoplasmosis likely has effects on depression given it alters brain-chemistry, however this has not been well-studied. Intuition would state that ‘Toxo’ would cause decreases due to its raising dopamine[24] however some case-studies have indicated that depressed patients become less responsive to depression-treatments when they are T. gondii -positive.[25]

Beneficial associations

Dopamine deficiency disorders such as in ADD and ADHD which affect cognitive performance may be improved by infection by toxoplasma. Studies confirm elevated dopamine metabolism given T. gondii infection [Emese Prandovszky e.t al., "The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine Metabolism"].[26] Although dopamine deficiency is not fully understood, it is known to be associated with polymorphism of the Dopamine Transporter gene (DAT1) on chromosome 5. DAT1 encodes the absorption of dopamine back to the cell through the cell membrane. The benefit that T. gondii offers is for people with DAT1 mutations that cause too fast absorption back to the cell (reuptake). Too fast dopamine absorption causes deficits that can be compensated either by elevated dopamine metabolism as T. gondii infection offers, or by slowing down the absorption as done by using prescribed Ritalin. Lately it was discovered that Premature Ejaculation is also caused by dopamine deficiency as a result of the DAT1 gene polymorphism.[27] This finding suggests that the elevated dopamine levels caused by T. gondii can help individuals who suffer from the premature ejaculation sexual dysfunction. However, individuals with positive RhD blood type are less affected by T. gondii infection and therefore the number of T. gondii cells in these individuals may not be sufficient to compensate for the fast reuptake due to genetic defects in the DAT1 Dopamine Transporter gene. Moreover, ADD and ADHD are related to Dementia with Lewy Body[28] , a fact that justifies additional research. Recent research shows that Toxoplasma gondii infection has a negative correlation with severeness and presence of Alzheimer’s [Bong-Kwang Jung et al., "Toxoplasma gondii Infection in the Brain Inhibits Neuronal Degeneration and Learning and Memory Impairments in a Murine Model of Alzheimer’s Disease"].[21] Dopamine deficiency is indirectly expressed by high availability of dopamine receptors also in neonatal development stages [29] Improvement in ADD/ADHD is verifiable by cognitive load tests and involves testing the Working Memory performance. Though, not all patients benefited T. gondii’s presence — (see Toxo’s detrimental associations.) Future studies of ADHD and ADD therefore should combine identification of Dopamine Transporter DAT1 mutations, presence or absence of T. gondii antibodies and cognitive tests.

Detrimental associations

Studies have shown behavioral changes in humans, including slower reaction times and a sixfold increased risk of traffic accidents among infected, RhD-negative males,[30] 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.[31][32] A study of 191 young women in 1999 reported higher intelligence and higher guilt proneness in Toxoplasma-positive subjects.[33]

The ability of Toxoplasma gondii to elevate dopamine levels may be detrimental to individuals whose brains already produce too much dopamine, e.g. schizophrenics. Enhancement in dopamine and glutamate levels may cause greater neuronal connectivity, in some cases leading to lower efficiency neurologically and metabolically. Synaptic pruning processes exist to minimize such inefficiencies [Julien Mayor & Kim Plunkett, "A neuro-computational account of taxonomic responding and fast mapping in early word learning"] but can be inhibited by some factors including dopamine level as seen in schizophrenia too diverse brain connectivity and insufficient global brain connectivity.[34] High metabolic costs imply more glial cells provide nourishment for the parasite which can’t reproduce in neurons[35] and allow for further infection in RhD negative patients[citation needed].


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. Edouard Chatton and G. Blanc suspected that T. gondii is spread via arthropods in 1917, but no evidence of this was found. [36] [37]

The first case of T.gondii infecting a human host was found in an infant girl who was delivered full-term by Caesarean section on May 23, 1938 at Babies Hospital, New York. The brain, spinal cord and the right eye were removed and examined to find T. gondii was found in lesions in the girl. [38] [39]

The possibility of transmission via undercooked meat was proposed by Weinman and Chandler in 1954 by testing the denaturing of the cysts in the muscle of animals. [40] This hypothesis was tested in Paris in 1965 by Desmonts, and it was found that 80% of the adults who ate undercooked meat tested positive for T. gondii antibodies, meaning the undercooked meat contained live T. gondii capable of infection compared to the fully cooked meat. [41] [42] During the same year, it was discovered that T. gondii can be spread via the fecal–oral route via cat to warm-blooded host by Hutchison. [43] The feces of an infected cat were observed, and eggs of T. gondii were isolated.

The first viable T. gondii was isolated by Albert Sabin in 1937 from laboratory mice. [44]


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