Toxoplasmosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

Pathophysiology

Toxoplasma gondii is a protozoan parasite that infects most species of warm blooded animals, including humans, causing the disease toxoplasmosis.

Members of the cat family (Felidae) are the only known definitive hosts for the sexual stages of T. gondii and thus are the main reservoirs of infection. Cats become infected with T. gondii by carnivorism . After tissue cysts or oocysts are ingested by the cat, viable organisms are released and invade epithelial cells of the small intestine where they undergo an asexual followed by a sexual cycle and then form oocysts, which are excreted. The unsporulated oocyst takes 1 to 5 days after excretion to sporulate (become infective). Although cats shed oocysts for only 1 to 2 weeks, large numbers may be shed. Oocysts can survive in the environment for several months and are remarkably resistant to disinfectants, freezing, and drying, but are killed by heating to 70°C for 10 minutes.

Transmission

Life cycle of Toxoplasma gondii

Transmission may occur through:

• Ingestion of raw or partly cooked meat, especially pork, lamb, or venison containing Toxoplasma cysts. Infection prevalence in countries where undercooked meat is traditionally eaten, such as France, has been related to this transmission method. Oocysts may also be ingested during hand-to-mouth contact after handling undercooked meat, or from using knives, utensils, or cutting boards contaminated by raw meat.

• Ingestion of contaminated cat faeces. This can occur through hand-to-mouth contact following gardening, cleaning a cat's litter box, contact with children's sandpits, or touching anything that has come into contact with cat faeces.
• Drinking water contaminated with Toxoplasma.
• Transplacental infection in utero.
• Receiving an infected organ transplant or blood transfusion, although this is extremely rare.
• Accidental inoculation of tachyzoites

Transplacental Transmission

• infection in 1st trimester - incidence of transplacental infection is low (15%) but disease in neonate is most severe.
• Infection in 3rd trimester - incidence of transplacental infection is high (65%) but infant is usually asymptomatic at birth.

The cyst form of the parasite is extremely hardy, capable of surviving exposure to freezing down to −12 degrees Celsius, moderate temperatures and chemical disinfectants such as bleach, and can survive in the environment for over a year. It is, however, susceptible to high temperatures—above 66 degrees Celsius, and is thus killed by thorough cooking, and would be killed by 24 hours in a typical domestic freezer.

Cats excrete the pathogen in their faeces for a number of weeks after contracting the disease, generally by eating an infected rodent. Even then, cat faeces are not generally contagious for the first day or two after excretion, after which the cyst 'ripens' and becomes potentially pathogenic. Studies have shown that only about 2% of cats are shedding oocysts at any one time, and that oocyst shedding does not recur even after repeated exposure to the parasite. Although the pathogen has been detected on the fur of cats, it has not been found in an infectious form, and direct infection from handling cats is generally believed to be very rare.

Associated Conditions

The parasite itself can cause various effects on the host body, some of which are not fully understood.

Reproductive changes

A recent study has indicated Toxoplasmosis correlates strongly with an increase in boy births in humans. According to the researchers, depending on the antibody concentration, the probability of the birth of a boy can increase up to a value of 0.72 ... which means that for every 260 boys born, 100 girls are born. The study also notes a mean rate of 0.60 to 0.65 (as opposed to the normal 0.51) for Toxoplasma positive mothers.

Behavioral changes

It has been found that the parasite has the ability to change the behavior of its host: infected rats and mice are less fearful of cats — in fact, some of the infected rats seek out cat-urine-marked areas. This effect is advantageous to the parasite, which will be able to sexually reproduce if its host is eaten by a cat. The mechanism for this change is not completely understood, but there is evidence that toxoplasmosis infection raises dopamine levels in infected mice.

The findings of behavioral alteration in rats and mice have led some scientists to speculate that toxoplasma may have similar effects in humans, even in the latent phase that had previously been considered asymptomatic. Toxoplasma is one of a number of parasites that may alter their host's behaviour as a part of their life cycle. The behaviors observed, if caused by the parasite, are likely due to infection and low-grade encephalitis, which is marked by the presence of cysts in the brain, which may produce or induce production of a neurotransmitter, possibly dopamine, therefore acting similarly to dopamine reuptake inhibitor type antidepressants and stimulants.

"In populations where this parasite is very common, mass personality modification could result in cultural change. [Variations in the prevalence of Toxoplasma gondii] may explain a substantial proportion of human population differences we see in cultural aspects that relate to ego, money, material possessions, work and rules." — Kevin Lafferty

Correlations have been found between latent Toxoplasma infections and various characteristics:

• Decreased novelty-seeking behaviour
• Slower reactions
• Lower rule-consciousness and jealousy (in men)
• More warmth and conscientiousness (in women)

The evidence for behavioral effects on humans is relatively weak. There have been no randomized clinical trials studying the effects of toxoplasma on human behavior. Although some researchers have found potentially important associations with toxoplasma, it is possible that these associations merely reflect factors that predispose certain types of people to infection (e.g., people who exhibit risk-taking behaviors may be more likely to take the risk of eating undercooked meat).

Studies have found that toxoplasmosis is associated with an increased car accident rate, roughly doubling or tripling the chance of an accident relative to uninfected people. This may be due to the slowed reaction times that are associated with infection. "If our data are true then about a million people a year die just because they are infected with toxoplasma," the researcher Jaroslav Flegr told The Guardian. The data shows that the risk decreases with time after infection, but is not due to age. Ruth Gilbert, medical coordinator of the European Multicentre Study on Congenital Toxoplasmosis, told BBC News Online these findings could be due to chance, or due to social and cultural factors associated with toxoplasma infection. However there is also evidence of a delayed effect which increases reaction times.

Other studies suggest that the parasite may influence personality. There are claims of toxoplasma causing antisocial attitudes in men and promiscuity (or even "signs of higher intelligence" ) in women, and greater susceptibility to schizophrenia and manic depression in all infected persons. A 2004 study found that toxoplasma "probably induce[s] a decrease of novelty seeking."

According to Sydney University of Technology infectious disease researcher Nicky Boulter in an article that appeared in the January/February 2007 edition of Australasian Science magazine, Toxoplasma infections lead to changes depending on the sex of the infected person.

IQ

The study suggests that male carriers have lower IQs, a tendency to achieve a lower level of education and have shorter attention spans, a greater likelihood of breaking rules and taking risks, and are more independent, anti-social, suspicious, jealous and morose. It also suggests that these men are deemed less attractive to women. Women carriers are suggested to be more outgoing, friendly, more promiscuous, and are considered more attractive to men compared with non-infected controls.

Schizophrenia

The possibility that toxoplasmosis is one cause of schizophrenia has been studied by scientists since at least 1953. These studies had attracted little attention from U.S. researchers until they were publicized through the work of prominent psychiatrist and advocate E. Fuller Torrey. In 2003, Torrey published a review of this literature, reporting that almost all the studies had found that schizophrenics have elevated rates of toxoplasma infection. A 2006 paper has even suggested that prevalence of toxoplasmosis has large-scale effects on national culture. These types of studies are suggestive but cannot confirm a causal relationship (because of the possibility, for example, that schizophrenia increases the likelihood of toxoplasma infection rather than the other way around).

• Acute Toxoplasma infection sometimes leads to psychotic symptoms not unlike schizophrenia.
• Some anti-psychotic medications that are used to treat schizophrenia, such as Haloperidol, also stop the growth of Toxoplasma in cell cultures.
• Several studies have found significantly higher levels of Toxoplasma antibodies in schizophrenia patients compared to the general population.
• Toxoplasma infection causes damage to astrocytes in the brain, and such damage is also seen in schizophrenia.

References

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