Toxoplasma gondii tachyzoites Source: http://upload.wikimedia.org/wikipedia/commons/3/39/Toxoplasma_gondii_tachy.jpg
Toxoplasma gondii is a single-celled eukaryotic protozoan parasite. The name for Toxoplasma is derived from the shapt of the organism, which is crescent-like (toxon is Greek for "arc"). T. gondii holds notoriety as the pathogen that causes the disease toxoplasmosis in humans. Infacts (especially via vertical transmission) and immuno-compromised hosts (including cats) are readily infected with the pathogen and show accelerated and concentrated symtoms, but it is interesting to observe that the pathogen is generally asymptomatic in healthy individuals with a competent immune system. Nearly one-third of the world's human population is infected with Toxoplasma, though this is the latent form of the disease and is non-fatal. The protozoan parasite preferentially encysts itself within the tissues of the brain and the central nervous system of the host. In extreme cases, Toxoplasma gondii can cause encephalopathy, loss of normal cognitive brain function, impaired judgment, peripheral neuropathy, slowed reflexes, pathological lesions, and other disorders classically associated with the invasion of the brain. Toxoplasma gondii has also been implicated in causing behavioral changes in its hosts!
Toxoplasmosis was discovered in 1908 and the pathogen itself was identified in the Noth African rodent Ctenodactylus gundi, as it was being used for research in the Pasteur Institute in Tunis. The complete lifecycle of T. gondii was not examined in its entirety until 1970. Research demonstrated that cats are the definitive host of the pathogen and Toxoplasma gondii parasites are excreted as oocytes in cat feces, while humans and other mammals are intermediate hosts. When encysted, Toxoplasma is very tough and resistant to low temperature extremes, even as low as -12˚C. Harsh agents (corrosives, such as bleach) also have minimal effects on Toxoplasma, as does direct sunlight. However, high temperatures (approximately 66˚C) can successfully destroy the protozoan.
In 1923, the first case of human toxoplasmosis was reported in an 11-month-old child. However, it is universally accepted that zoonosis (the proceess by which a disease is passed from animals to humans) occured much farther back in time than this first recorded case. The parasite originated from animals hosts that were in close contact with humans, most notably cats (even though, as noted above, T. gondii can infect several other mammals and birds). T. gondii mainly spreads via contaminated cat feces, consumption of undercooked meat, tainted water, and vertical transmission.
Check out this short video for a nice overview!
Life Cycle[]
The only known definitive hosts for Toxoplasma gondii are members of the family Felidae (domestic cats and their relatives). Unsporulated oocysts are shed in the cat's feces. Although oocysts are usually shed for 1-2 weeks, large numbers may be shed. Oocysts take 1-5 days to sporulate in the environment and become infective. Intermediate hosts in nature (including birds and rodents) become infected after ingesting soil, water, or plant material contaminated with oocysts. Oocysts tranform into tachyzoites shortly after ingestion. These tachyzoites localize in neural and muscle tissue and develop into tissue cysts, bradyzoites.
Cats acquire Toxoplasma by ingesting any of three infectious stages of the organism: the rapidly multiplying forms called tachyzoites, the quiescent bradyzoites that occupy cysts in infected tissue, and the oocysts in the feces. Successful infection of the cat is revealed by the shedding of oocysts in the feces. The chance of infection and the prepatent period (the time between infection and the shedding of oocysts) varies with the stage of Toxoplasma gondii ingested. Fewer than 50 percent of cats shed oocysts after ingesting tachyzoites or oocysts, whereas nearly all cats shed oocysts after ingesting tissue cysts.
Humans can become infected by several routes:
- eating underbooked meat of animals harboring tissue cysts
- consuming food or water contaminated with cat feces of by contaminated environment samples (such as fecal-contaminated soil or changing the litter box of a pet cat)
- trans-placentally from mother to fetus
In the human host, the parasites form tissue cysts, most commonly in skeletal muscles, myocardium, brain, and eyes. These cysts may remain throughout the life of the host.
Toxoplasma gondii life cycle
Symptoms and Pathology[]
Symptoms of a Toxoplasma gondii infection may vary. Most people who become infected with Toxoplasma are not aware of it. Some people who have toxoplasmosis may feel as if they have the flu with swollen lymph glands or muscle aches and pains that last for a month or more. In humans, severe disease is usually observed only in congenitally infected children and in immunosuppressed individuals, including patients with AIDS.
Individuals who have weak immune systems often have severe cases of toxoplasmosis, though occasionally, even persons with healthy immune systems may experience eye damage from toxoplasmosis. Signs and symptoms of ocular toxoplasmosis can include reduced vision, blurred vision, pain (often with bright light), redness of the eye, and sometimes tearing. Severe toxoplasmosis, causing damage to the brain, eyes, or other organs, can develop from an acute Toxoplasma infection or one that had occurred earlier in life and is now reactivated. Encephalitis is an important and severe manifestation of toxoplasmosis in immunosuppressed patients.
Most infants who are infected while still in the womb have no symptoms at birth, but they may develop symptoms later in life. A small percentage of infected newborns have serious eye or brain damage at birth. Prenatally acquired Toxoplasma gondii infects the brain and retina and can cause a wide spectrum of clinical disease. Mild disease may consist of slightly diminished vision, whereas severly diseased children may exhibit more extreme signs: reinochoroiditis, hydrocephalus, convulsions, and intracerebral calcifications.
Girl with hydrocephalus due to congenital toxoplasmosis
The pathology of Toxoplasma gondii infection also varies greatly. Toxoplasma gondii may spread both locally to the lymph nodes and to distant organs by invading the lymphatics and blood. The level of pathology is determined by the extent of injury to organs, especially to vital and vulnerable organs, such as the eye, heart, and adrenals. Toxoplasma gondii does not produce a toxin; necrosis is caused by intracellular multiplication of tachyzoites.
Toxoplasma gondii causes disease through cell necrosis. This necrosis occurs due to reproduction. Tachyzoites reproduce in large numbers within a cell, eventually bursting from it. The interaction between T. gondii and the host immune system is widely studied and it has been demonstrated that the organism is able to cause disease by modulating the host immune response. The parasite induces an IL-12-linked immune response, which serves to control the abundance of active tachyzoites in the host. This contributes to the host's survival, which provides greater opportunity for spreading of the pathogen.
Diagnosis and Treatment[]
Diagnosis of Toxoplasma gondii infection is usually achieved through serology, although tissue cysts may be observed in stain biopsy specimen. Diagnosis of congenital infections can be achieved by detecting Toxoplasma gondii DNA in amniotic fluid using molecular techniques, such as PCR. Clinical signs of toxoplasmosis are nonspecific and cannot be depended on for a definite diagnosis because toxoplasmosis clinically mimics several other infectious diseases.
Many serologic tests have been used to detect antibodies to Toxoplasma gondii. The most reliable of these is the Sabin-Feldman dye test. Live virulent tachyzoites of T. gondii are used as antigens and are exposed to dilutions of the test serum and to complement accessory factor resembling complement that is obtained from Toxoplasma-antibody free-human serum. This test is sensitive and highly-specific, but it has a high cost.
Most healthy people recover from toxoplasmosis without treatment. Persons who are ill can be treated with a combination of drugs, such as pyrimethamine and sulfadiazine. They act synergistically by blocking the metabolic pathway involving p-aminobenzoic acid and the folic-folinic acid cycle, respectively. Although these drugs are helpful when given in the acute stage of the disease, usually they will not eradicate infection when active multiplication of the parasite occurs. Therefore, they must be administered in daily divided doses. Pregnant women, newborns, and infacts can also be treated, although the parasite is not eliminated completley. The parasites can remain within tissue cells in a less active phase, therefore their location makes it difficult for the medication to completley eliminate them.
Use of Pyrimethamine against T. gondii
Persons with ocular toxoplasmosis are sometimes prescribed medicine to treat active disease by their ophthalmologist. Whether or not medication is recommended depends on the size of the eye lesion, the location, and the characteristics of the lesion (acute active versus chronic not progressing). Persons with compromised immune systems need not be treated until they have improvement in their condition. For AIDS patients, continuation of medication for the rest of their lives may be necessary, or for as long as they are immunosuppressed.
No killed vaccine is currently available to reduce or prevent congenital infections in humans and animals, but research to develop such an agent is under way.
Host Manipulation[]
The parasite Toxoplasma gondii manipulates the behavior of its intermediate rat host
T. gondii intermediate host manipulation
in order to increase its chances of being predated by cats, its feline definitive host, thereby ensuring the completion of its life cycle. Toxoplasma gondii's manipulation appears to alter the rat's perception of cat predation risk. For instance, mice and rats (common intermediate hosts for Toxoplasmosis) have a strong aversion to the smell of cat urine, as it is indicative of the presence of a cat (or to a mouse, a predator) in the immediate vicinity.
A study by Vyas et. al. found that T. gondii has developed a mechanism by which it changes rodent's innate aversion to feline odors and instead produces an attraction to these smells, this increasing the likelihood that the intermediate rodent host will be eaten by the feline definitive host. This adaptation of T. gondii aids in its transmission to a definitive host, and ensures its ability to reproduce sexually. The mechanisms by which T. gondii is able to make such behavior modifications in the host are still unknow. The selectivity of such behavioral changes suggests that this ubiquitous parasite subtly alters the brain of its intermediate host to enhance predation rate while leaving other behavioral categories and general health intact.
While the symptoms of Toxoplasma infection seem to be fairly mild, recent research regarding this parasite has revealed an abundance of information pertaining to the psychological effects that Toxoplasmosis infection can induce in a human host. Toxoplasma infection has been linked to increased risk of developing schizophrenia in infants whose mothers were infected by Toxoplasmosis, correlated to differences in behaviors between cultures, linked to increased neuroticism,and an alarmingly high correlation between infection and suicide rates. In one specific study from Wilcox, scientists were able to measure antibody levels against T. gondii from children to determine both the mother's infection status (because children's antibodies reflect those of their mothers until about three months after birth), and use a cause of death register to passively screen the relationship between Toxoplasmosis infection and self-directed violence and suicide. The correlation between Toxoplasmosis infection and suicide was alarmingly high, the mother of the children that had ben screened with Toxoplasmosis were 54% more likely to have attempted suicide, and two times as likely to have succeeded in that endeavor. Specifically, women infected with Toxoplasmosis were more likely to have attempted (or succeeded in) committing suicide violently. Additionally, it was determined that those with the highest levels of antibody serum were even more likely to commit a violent suicide (91%) than women with lower levels of antibody serum or uninfected women. This new information regarding Toxoplasmosis infection is alarming, and especially so because scientists do not fully understand the mechanisms by which T. gondii is able to hijack the brain's neurochemical pathways to significantly alter human behavior.
Epidemiology[]
Toxoplasma gondii infection in humans is widespread throughout the world. Approximately half a billion humans have antibodies to T. gondii. The incidence of infection in humans and animals may vary in different parts of a country. The cause for these variations is not yet known: environmental conditions, cultural habits, and animal species are among factors that may determine the degree of natural spread of Toxoplasma gondii. People typically become infected with Toxoplasma by three principal routes of transmission: foodborne, animal-to-human (zoonotic), and mother-to-child (congenital).
The tissue form of the parasite (a microscopic cyst consisting of bradyzoites) can be transmitted to humans by food. People become infected after:
- eating undercooked, contaminated meat (especially pork, lamb, and venison)
- accidental ingestion of undercooked, contaminated meat after handling it and not washing hands thoroughly (Toxoplasma cannot be absorbed through intact skin)
- eating food that was contaminated by knives, utensils, cutting boards, or other foods that had contact with raw, contaminated meat
Cats play an important role in the spread of toxoplasmosis. Cats become infected by eating infected rodents, birds, or other small animals. The parasite is then passed in the cat's feces in an oocyst form. Kittens and cats can shed millions of oocysts in their feces for as long as 3 weeks after infection. Mature cats are less likely to shed Toxoplasma if they have been previously infected. A Toxoplasma-infected cat that is shedding the parasite in its feces contaminated the litter box. If the cat is allowed outside, it can contaminate the soil or water in the environment as well.
Toxoplasma can be transmitted to people via cats through people accidentally swallowing the oocyst for of the parasite. People can be infected by:
- accidental ingestion of oocysts after cleaning a cat's litter box when the cat has shed Toxoplasma in its feces
- accidental ingestion of oocysts after touching or ingesting anything that has come in contact with a cat's feces that contain Toxoplasma
- accidental ingestion of oocysts in contaminated soil (not washing hands after gardening or eating unwashed fruits or vegetables from the garden)
A mother who is newly infected with Toxoplasma gondii during pregnancy can pass the infection on to her unborn child (congenital infection). The woman may not have symptoms, but there can be severe consequences for the unborn child, such as disease of the nervous system and the eyes.
Prevention and Control[]
People who are healthy should follow the guidelines below to reduce the risk of toxoplasmosis. First is toreduce the risk from food. Food should be cooked to safe temperatures. Freeze meat for several days at sub-zero temperatures before cooking to greatly reduce the chances of infection. Peel or wash fruits and vegetables thoroughly before eating. Wash cutting boards, dishes, counters, utensils, and hands with hot, soapy water after contact with raw meat, poultry, seafood, or unwashed fruits and vegetables.
Secondly, people can reduce their risk from the environment. Avoid drinking untreated drinking water. Wear
gloves when gardening and during contact with soil or sand because it might be contaminated with cat feces. Wash hands with soap and warm water after gardening or contact with soil or sand. Teach children the importance of washing hands to prevent infection. Keep outdoor sandboxes covered. Feed cats only canned or dried commercial food or well-cooked table food, not raw or undercooked meats.
Change the litter box daily if you own a cat. The Toxoplasma parasite does not become infectious until 1 to 5 days after it is shed in a cat's feces. If you are pregnant or immunocompromised, avoid changing cat
litter if possible. If no one else can preform the task, wear disposable gloves and wash your hands with soap and warm water afterwards. Keep cats indoors. Do not adopt or handle stray cats, especially kittens. Do not get a new cat if you are pregnant.
Current Research[]
Effects of T. gondii on personality traits of humans
Jaroslav Flegr and his colleagues have been studying the effects of T. gondii infection on human personality traits and behavior. Utilizing university students, military recruits, and blood donors, Flegr has administered a series of personality questionnaires and compared individuals with and without antibodies to T. gondii. Infected men were shown to be more expedient, suspicious, jealous, and dogmatic, whereas infected women had more warmth and superego strength. Thus, sex differences of the effect of T. gondii in humans have been shown. Flegr's article "Effects of Toxoplasma on human behavior" has been criticized for its sample population and validity of the questionaires in measuring personality traits.
Effects of T. gondii on the behavior of humans
In another study by Flegr, "Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study," the sera of 146 individuals deemed to have been responsible for causing a motor vehical accident were compared with 446 controls. Those individuals who had antibodies to T. gondii, compared with those without antibodies, had more than twice the risk of having caused a motor vehicle accident. The findings of this study were replicated by another cohort in the Czech Republic.
Studies of antibodies in individuals who have schizophrenia
Antibody studies provide among the strongest evidence linking T. gondii to schizophrenia.
A 2012 updated meta-analysis by Torrey et. al. of 38 studies included 6,067 individuals with schizophrenia and 8,715 controls. The meta-analysis also reported an odds ratio of OR 2.71 (1.93-3.80). In other words, if a person has been infected with T. gondii, he/she has a 2.71 times greater chance of having schizophrenia than if the person had not been infected. These studies were done in 14 different countried; this, the finding of increased antibodies against T. gondii in individuals with schizophrenia has been remarkably consistent geographically and over half a century.
Sources[]
- CDC: Centers for Disease Control and Prevention. "Parasites - Toxoplasmosis (Toxoplasma Infection)."
- Dubey, J. 1996. "Chapter 84: Toxoplasma Gondii." Medical Microbiology, 4th Edition.
- Flegr, J. 2007. "Effects of Toxoplasma on human behavior. Schizophr Bull; 33: 757-760.
- Flegr, J. et. al. 2002. "Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective cast-control study." BMC Infect Dis;2:11.
- Kang et. al. 2004. "Toxoplasma gondii-derived heat shock protein 70 stimulates the maturation of human monocyte-derived dendritic cells." Biochemical and biophysical research communications, 322.
- The Mayo Clinic Staff. Toxoplasmosis: Treatment and Drugs.
- Torrey, E. et. al. 2012. "Toxoplasma gondii: meta-analysis and assessment as a risk factor for schizophrenia." Schizophr Bull; 38:642-647.
- Vyas, A. et. al. 2007. Behavioral changes induced by Toxoplasma infection of rodents are highlt specific to aversion of cat odors.
- Wilcox, C. 2012. "Toxoplasma's Dark Side: The Link Between Parasite and Suicide." Scientific American.