Toxoplasmosis Classification and external resources
T. gondii tachyzoites
ICD-10 B58 ICD-9 130 DiseasesDB 13208 MedlinePlus 000637 eMedicine med/2294 MeSH D014123
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. Cats are the primary source of infection to human hosts, although contact with raw meat, especially pork, is a more significant source of human infections in some countries. Fecal contamination of hands is a significant 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). Recent research has also linked toxoplasmosis with brain cancer.
- 1 Signs and symptoms
- 2 Diagnosis
- 3 Transmission
- 4 Treatment
- 5 Biological modifications of the host
- 6 Epidemiology
- 7 History
- 8 Society and culture
- 9 See also
- 10 References
- 11 External links
Signs and symptoms
Infection has two stages:
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.
It is easy for a host to become infected with Toxoplasma gondii and develop toxoplasmosis without knowing it. In most immunocompetent patients, the infection enters a latent phase, during which only bradyzoites are present, forming cysts in nervous and muscle tissue. Most infants who are infected while in the womb have no symptoms at birth but may develop symptoms later in life.
While rare, skin lesions may occur in the acquired form of the disease, including roseola and erythema multiforme-like eruptions, prurigo-like nodules, urticaria, and maculopapular lesions. Newborns may have punctate macules, ecchymoses, or “blueberry muffin” lesions. Diagnosis of cutaneous toxoplasmosis is based on the tachyzoite form of T. gondii being found in the epidermis. It is found in all levels of the epidermis, is about 6 μm by 2 μm , bow-shaped, the nucleus being one-third of its size. It can be identified by electron microscopy or by Giemsa staining tissue where the cytoplasm shows blue, the nucleus red.
Studies have been conducted that show the toxoplasmosis parasite may affect behavior and may present as or be a causative or contributory factor in various psychiatric disorders such as depression, anxiety and schizophrenia. In 11 of 19 scientific studies, T. gondii antibody levels were found to be significantly higher in individuals affected by first-incidence schizophrenia than in unaffected persons. Individuals with schizophrenia are also more likely to report a clinical history of toxoplasmosis than those in the general population. Recent work at the University of Leeds has found that the parasite produces an enzyme with tyrosine hydroxylase and phenylalanine hydroxylase activity. This enzyme may contribute to the behavioral changes observed in toxoplasmosis by altering the production of dopamine, a neurotransmitter involved in mood, sociability, attention, motivation and sleep patterns. Schizophrenia has long been linked to dopamine dysregulation.
Toxoplasmosis can be difficult to distinguish from that of primary central nervous system lymphoma, and as a result, the diagnosis is made by a trial of therapy (pyrimethamine, sulfadiazine + leucovorin), or a brain biopsy if the drugs produce no effect.
Toxoplasmosis cannot 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 a 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.
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.
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.
Treatment is often only recommended for people with serious health problems or with HIV with CD4 count under 200, because the disease is most serious when one's immune system is weak. Trimethoprim/sulfamethoxazole is the drug of choice to prevent Toxoplasma, but is not the drug to treat.
Medications that are prescribed for acute toxoplasmosis are:
- Pyrimethamine — an antimalarial medication.
- Sulfadiazine — an antibiotic used in combination with pyrimethamine to treat toxoplasmosis.
- Combination therapy is usually given with folinic acid supplements to reduce incidence of thrombocytopaenia.
- clindamycin — an antibiotic used most often for people with HIV/AIDS.
- spiramycin — an antibiotic used most often for pregnant women to prevent the infection of their child.
In people with latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics do not reach the bradyzoites in sufficient concentration.
Medications that are prescribed for latent toxoplasmosis are:
- atovaquone — an antibiotic that has been used to kill Toxoplasma cysts inside AIDS patients.
- clindamycin — an antibiotic which, in combination with atovaquone, seemed to optimally kill cysts in mice.
Biological modifications of the host
The parasite itself can cause various effects on the host body, some of which are not fully understood.
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 is able to proliferate if a cat eats the infected rat and thereby becomes a carrier. 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.
Toxoplasma's role in schizophrenia
The possibility that toxoplasmosis is one cause of schizophrenia has been studied by scientists since 1953. These studies 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.
- 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.
The U.S. NHANES (1999–2004) national probability sample found that 10.8% of U.S. persons 6–49 years of age, and 11.0% of women 15–44 years of age, had Toxoplasma-specific IgG antibodies, indicating that they were infected with the organism. This prevalence has significantly decreased from the NHANES III (1988–1994).
It is estimated that between 30% and 65% of all people worldwide are infected with toxoplasmosis. However, there is large variation between countries: in France, for example, around 88% of the population are carriers, probably due to a high consumption of raw and lightly cooked meat.  Germany, the Netherlands and Brazil also have high prevalences of around 68%, over 80% and 67% respectively. In Britain about 22% are carriers, and South Korea's rate is 4.3%.
Two risk factors for contracting toxoplasmosis are:
- Infants born to mothers who became infected with Toxoplasma for the first time during or just before pregnancy.
- Persons with severely weakened immune systems, such as those with AIDS. Illness may result from an acute Toxoplasma infection or reactivation of an infection that occurred earlier in life.
In other animals
A University of California, Davis study of dead sea otters collected from 1998 to 2004 found that toxoplasmosis was the cause of death for 13% of the animals. Proximity to freshwater outflows into the ocean was a major risk factor. Ingestion of oocysts from cat faeces is considered to be the most likely ultimate source. Runoff containing wild cat faeces and litter from domestic cats flushed down toilets are possible sources of oocysts. According to an article in New Scientist the parasites have been found in dolphins and whales. Researchers Black and Massie believe that anchovies, which travel from estuaries into the open ocean, may be helping to spread the disease.
The protozoan was first discovered by Nicolle & Manceaux, who in 1908 isolated it from the African rodent Ctenodactylus gundi, then in 1909 differentiated the disease from Leishmania and named it Toxoplasma gondii. The first recorded congenital case was not until 1923, and the first adult case not until 1940. In 1948, a serological dye test was created by Sabin & Feldman, which is now the standard basis for diagnostic tests.
Society and culture
- Arthur Ashe (tennis player) developed neurological problems from toxoplasmosis (and was later found to be HIV-positive).
- Merritt Butrick (actor) was H.I.V positive. Died from toxoplasmosis as a result of his already weakened immune system.
- Prince François, Count of Clermont (pretender to the Throne of France); his disability has caused him to be overlooked in the line of succession.
- Leslie Ash (actress) contracted toxoplasmosis in the second month of pregnancy.
- Sebastian Coe (British middle distance runner)
- Martina Navrátilová (tennis player) retired from a competition in 1982 with symptoms of a mystery 'virus' that were later found to be due to toxoplasmosis.
- Louis Wain (artist) was famous for painting cats; he later developed schizophrenia, which some believe was due to toxoplasmosis resulting from his prolonged exposure to cats.
Literature and film
- The effects of Toxoplasmosis on human behavior is central to the plot of Kitty Kitty, a film directed by Michael Medaglia in 2011.
- Toxoplasmosis is referred to at the end of the British TV series Doc Martin, Series 4, Episode 6: "MidWife Crisis", first broadcast on 25 October 2009. This was in relation to eating roadkill, including "Badger Burgers".
- Toxoplasmosis is referred to in the seventeenth episode of the first season of House M.D. entitled "Role Model."
- Toxoplasmosis is often referenced in Peeps, a 2005 novel by Scott Westerfeld.
- In the 1996 film Trainspotting, the character Tommy, a heroin addict with AIDS, acquires toxoplasmosis and dies.
- Toxoplasmosis is referenced in And The Band Played On, a 1993 American television film docudrama directed by Roger Spottiswoode. The teleplay by Arnold Schulman is based on the best-selling 1987 non-fiction book And the Band Played On: Politics, People, and the AIDS Epidemic by Randy Shilts.
- Toxoplasmosis was the subject of a controversial story line in the early years of the American television soap opera "All My Children" (1973–1974) in which a then-teenage Erica Kane (Susan Lucci) developed a nearly fatal case of Toxoplasmosis after an abortion. It was later explained to have been caused by the changing of a cat litter box.
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- ^ Conrad P, Miller M, Kreuder C, James E, Mazet J, Dabritz H, Jessup D, Gulland F, Grigg M (2005). "Transmission of Toxoplasma: clues from the study of sea otters as sentinels of Toxoplasma gondii flow into the marine environment". Int J Parasitol 35 (11–12): 1155–68. doi:10.1016/j.ijpara.2005.07.002. PMID 16157341.
- ^ 17:30-22:00 "Treating Disease in the Developing World". Talk of the Nation Science Friday. National Public Radio. December 16, 2005. http://www.npr.org/templates/story/story.php?storyId=5058325 17:30-22:00.
- ^ "Parasite in cats killing sea otters". NOAA magazine (National Oceanic and Atmospheric Administration). 21 January 2003. http://www.magazine.noaa.gov/stories/mag72.htm. Retrieved 24 November 2007.
- ^ http://www.newscientist.com/article/mg20427301.600-3-schizophrenia.html
- ^ Toxoplasma Serology Laboratory: Laboratory Tests For The Diagnosis Of Toxoplasmosis
- ^ Arthur Ashe, Tennis Star, is Dead at 49 New York Times (02/08/93)
- ^ Merritt Butrick, A Biography Angelfire.com, accessdate Mar 18, 2011
- ^ "Pregnancy superfoods revealed". BBC News. January 10, 2001. http://news.bbc.co.uk/1/hi/health/1109818.stm. Retrieved May 25, 2010.
- ^ "Olympics bid Coes finest race". The Times (London). June 26, 2005. http://www.timesonline.co.uk/tol/sport/article537461.ece. Retrieved May 25, 2010.
- ^ Sonja Matthee: Parasite of the month: Toxoplasma gondii. November 16, 1998.
- ^ "Topic 33. Coccidia and Cryptosporidium spp". Biology 625: Animal Parasitology. Kent State Parasitology Lab. October 24, 2005. http://www.k-state.edu/parasitology/classes/625protozoa33.html. Retrieved 2006-10-14. Includes a list of famous victims.
- Parts of this article are taken from the public domain CDC factsheet: Toxoplasmosis
- Toxoplasmosis at Merck Manual of Diagnosis and Therapy Professional Edition
- Health Protection Agency (HPA), UK: Toxoplasmosis.
- Pictures of Toxoplasmosis Medical Image Database
Infectious diseases – Parasitic disease: protozoan infection: Chromalveolate and Archaeplastida (A07, B50–B54,B58, 007, 084) Chromalveolate ArchaeplastidaAlgaemia: Prototheca wickerhamii (Protothecosis)
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