Understanding and definition of Toxoplasmosis

Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid (cat) family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself recently been infected, or by transmission from mother to fetus. Although cats are often blamed for spreading
toxoplasmosis, contact with raw meat is a more significant source of human infections in Africa and fecal contamination of hands is a greater risk factor.

Up to one third of the world's human population is estimated to carry a Toxoplasma infection. The Centers for Disease Control and Prevention notes that overall seroprevalence in the United States as determined with specimens collected by the National Health and Nutritional Examination Survey (NHANES) between 1999 and 2004 was found to be 10.8%, with seroprevalence among women of childbearing age (15 to 44 years) 11%.

During the first few weeks post-exposure, the infection typically causes a mild flu-like illness or no illness. Thereafter, the parasite rarely causes any symptoms in otherwise healthy adults. However, those with a weakened immune system, such as AIDS patients or pregnant women, may become seriously ill, and it can occasionally be fatal. The parasite can cause encephalitis (inflammation of the brain) and neurologic diseases, and can affect the heart, liver, inner ears, and eyes (chorioretinitis).

During acute toxoplasmosis, symptoms are often influenza-like: swollen lymph nodes, or muscle aches and pains that last for a month or more. Rarely, a patient with a fully functioning immune system may develop eye damage from toxoplasmosis. Young children and immunocompromised patients, such as those with HIV/AIDS, those taking certain types of chemotherapy, or those who have recently received an organ transplant, may develop severe toxoplasmosis. This can cause damage to the brain (encephalitis) or the eyes (necrotizing retinochoroiditis). Infants infected via placental transmission may be born with either of these problems, or with nasal malformations, although these complications are rare in newborns.

Swollen lymph nodes are more commonly found in the neck followed by axillae and then groin. Swelling may occur at different times after the initial infection, persist, and/or recur for various times independently of antiparasitic treatment. It is usually found at single sites in adults, but in children multiple sites may be more common. Enlarged lymph nodes will resolve within one to two months in 60% of patients. However, a quarter of patients take 2–4 months to return to normal and 8% take 4–6 months. A substantial number of patients (6%) do not return to normal until much later.

Toxoplasmosis can be difficult to distinguish from that of primary central nervous system lymphoma, and , as a result, the diagnosis is either made by a trail of therapy (pyrimethamine, sulfadiazine + leucovorin. If treatment fails, brain biopsy is indicated.

Detection of Toxoplasma gondii in human blood samples may also be achieved by using the polymerase chain reaction (PCR). Inactive cysts may exist in a host which would evade detection.

Toxoplasmosis can't be detected with immunostaining. Lymph nodes affected by toxoplasma have characteristic changes, including poorly demarcated reactive germinal centers, clusters of monocytoid B cells and scattered epithelioid histiocytes.

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 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 feces. This can occur through hand-to-mouth contact following gardening, cleaning a cat's litter box, contact with children's sandpits, or touching leach, and can survive in the environment for over a year. It is, however, susceptible to high temperatures—above 66 degrees Celsius (150 degrees Fahrenheit), 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 feces 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.

Congenital toxoplasmosis is a special form in which an unborn child is infected via the placenta. A positive antibody titer indicates previous exposure and immunity and largely ensures the unborn baby's safety. A simple blood draw at the first pre-natal doctor visit can determine whether or not the woman has had previous exposure and therefore whether or not she is at risk. If a woman receives her first exposure to toxoplasmosis while pregnant, the baby is at particular risk. A woman with no previous exposure should avoid handling raw meat, exposure to cat feces, and gardening (cat feces are common in garden soil). Most cats are not actively shedding oocysts and so are not a danger, but the risk may be reduced further by having the litterbox emptied daily (oocysts require longer than a single day to become infective), and by having someone else empty the litterbox. However, while risks can be minimized, they cannot be eliminated. For pregnant women with negative antibody titer, indicating no previous exposure to T. gondii, as frequent as monthly serology testing is advisable as treatment during pregnancy for those women exposed to T. gondii for the first time decreases dramatically the risk of passing the parasite to the fetus.

Despite these risks, pregnant women are not routinely screened for toxoplasmosis in most countries (Portugal, France, Austria, Uruguay, and Italy being the exceptions) for reasons of cost-effectiveness and the high number of false positives generated. As invasive prenatal testing incurs some risk to the fetus (18.5 pregnancy losses per toxoplasmosis case prevented), postnatal or neonatal screening is preferred. The exceptions are cases where fetal abnormalities are noted, and thus screening can be targeted.

Some regional screening programmes operate in Germany, Switzerland and Belgium.

Treatment is very important for recently infected pregnant women, to prevent infection of the fetus. Since a baby's immune system does not develop fully for the first year of life, and the resilient cysts that form throughout the body are very difficult to eradicate with anti-protozoans, an infection can be very serious in the young.

A recent study has indicated toxoplasmosis correlates strongly with an increase in male 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 0.608 (as opposed to the normal 0.51) for Toxoplasma-positive mothers. The study explains that this effect may not significantly influence the actual sex ratio of children born in countries with high rates of latent toxoplasmosis infection because "In high-prevalence countries, most women of reproductive age have already been infected for a long time and therefore have only low titres of anti-Toxoplasma antibodies. Our results suggest that low-titre women have similar sex ratios to Toxoplasma-negative women."

It has been found that the parasite has the ability to change the behaviour 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 proliferate as a cat could eat the infected rat and later reproduce. The mechanism for this change is not completely understood, but there is evidence that toxoplasmosis infection raises dopamine levels and concentrates in the amygdala in infected mice.

The findings of behavioural 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 human brain, which may produce or induce production of a neurotransmitter, possibly dopamine, therefore acting similarly to dopamine reuptake inhibitor type antidepressants and stimulants.

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

• Decreased novelty seeking behaviour
• Slower reactions
• Lower rule-consciousness and greater jealousy (in men)
• Greater warmth, conscientiousness and moralistic behavior (in women)

The evidence for behavioral effects on humans is controversial. No prospective research has been done on the topic, e.g., testing people before and after infection to ensure that the proposed behavior arises only afterwards. Although some researchers have found potentially important associations with Toxoplasma, the causal relationship, if any, is unknown, i.e., it is possible that these associations merely reflect factors that predispose certain types of people to infection. However, many of the neurobehavioral symptoms that are postulated to be due to toxoplasmosis correlate to the general function of dopamine in the human brain, and the fact that toxoplasma encodes the dopamine synthetic enzyme tyrosine hydroxylase enzymes makes it likely that neurobehavioral symptoms can result from infection.

Studies have found that toxoplasmosis is associated with an increased car accident rate in people with Rh-negative blood. The chance of an accident relative to uninfected people is increased roughly 2.5 times.

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 bipolar disorder 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.

The study suggests that male carriers 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. Female carriers are suggested to be more outgoing, friendly, more promiscuous, and are considered more attractive to men compared with non-infected controls. The results are shown to be true when tested on mice, though it is still inconclusive. A few scientists have suggested that, if these effects are genuine, prevalence of toxoplasmosis could be a major determinant of cultural differences.