Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, infected individuals may experience a few weeks or months of mild, flu-like illness such as muscle aches and tender lymph nodes. In a small number of people, eye problems may develop. In those with a weakened immune system, severe symptoms such as seizures and poor coordination may occur. If a woman becomes infected during pregnancy, a condition known as congenital toxoplasmosis may affect the child.
Toxoplasmosis is usually spread by eating poorly cooked food that contains cysts, by exposure to infected cat feces, or from an infected woman to her baby during pregnancy. Rarely, the disease may be spread by blood transfusion or other organ transplant. It is thought to not otherwise spread between people, but broader transmissibility remains a matter of scientific debate. Studies have reported the presence of T. gondii in human semen and have proposed sexual transmission as a possible route, though this has not been established as a primary mode of spread. The parasite is only known to reproduce sexually in the cat family. It can infect most types of warm-blooded animals, including humans. Diagnosis is typically by testing blood for antibodies or by testing the amniotic fluid in a pregnant patient for the parasite's DNA.
Prevention is by properly preparing and cooking food. Pregnant women are also recommended not to clean cat litter boxes or, if they must, to wear gloves and wash their hands afterwards. Treatment of otherwise healthy people is usually not needed. During pregnancy, spiramycin or pyrimethamine/sulfadiazine and folinic acid may be used for treatment.
Up to half of the world's population is infected by T. gondii, but have no symptoms. In the United States, approximately 11% of people have been infected, while in some areas of the world this is more than 60%. Approximately 200,000 cases of congenital toxoplasmosis occur yearly. Charles Nicolle and Louis Manceaux first described the organism in 1908. In 1941, transmission during pregnancy from a pregnant woman to her baby was confirmed. There is tentative evidence that otherwise asymptomatic infection may affect people's behavior.
Signs and symptoms Infection has three stages:
Acute Acute toxoplasmosis is often asymptomatic in healthy adults. However, symptoms may manifest and are often influenza-like: swollen lymph nodes, headaches, fever, and fatigue, or muscle aches and pains that last for a month or more. It is rare for a human with a fully functioning immune system to develop severe symptoms following infection. People with weakened immune systems are likely to experience headache, confusion, poor coordination, seizures, lung problems that may resemble tuberculosis or Pneumocystis jirovecii pneumonia (a common opportunistic infection that occurs in people with AIDS), or chorioretinitis caused by severe inflammation of the retina (ocular toxoplasmosis). Young children and immunocompromised people, 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. The toxoplasmic trophozoites causing acute toxoplasmosis are referred to as tachyzoites, and are typically found in various tissues and body fluids, but rarely in blood or cerebrospinal fluid.
Swollen lymph nodes are commonly found in the neck or under the chin, followed by the armpits and the groin. Swelling may occur at different times after the initial infection, persist, and 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 1–2 months in 60% of cases. However, a quarter of those affected take 2–4 months to return to normal, and 8% take 4–6 months. A substantial number (6%) do not return to normal until much later.
Latent Due to the absence of obvious symptoms, hosts easily become infected with T. gondii and develop toxoplasmosis without knowing it. Although mild, flu-like symptoms occasionally occur during the first few weeks following exposure, infection with T. gondii produces no readily observable symptoms in healthy human adults. When the infection enters a latent phase, during which only bradyzoites (in tissue cysts) are present; these tissue cysts and even lesions can occur in the retinas, alveolar lining of the lungs (where an acute infection may mimic a Pneumocystis jirovecii infection), heart, skeletal muscle, and the central nervous system (CNS), including the brain. Cysts form in the CNS (brain tissue) upon infection with T. gondii and persist for the lifetime of the host. Most infants who are infected while in the womb have no symptoms at birth, but may develop symptoms later in life.Randall Parker: Humans Get Personality Altering Infections From Cats . September 30, 2003
Reviews of serological studies have estimated that 30–50% of the global population has been exposed to and may be chronically infected with latent toxoplasmosis, although infection rates differ significantly from country to country. This latent state of infection has recently been associated with numerous disease burdens, neural alterations, and subtle sex-dependent behavioral changes in immunocompetent humans, as well as an increased risk of motor vehicle collisions.
Skin 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 by 2 μm and bow-shaped, with 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.
Cause
Parasitology In its lifecycle, T. gondii adopts several forms. Tachyzoites are responsible for acute infection; they divide rapidly and spread through the tissues of the body. Tachyzoites are also known as "tachyzoic merozoites", a descriptive term that conveys more precisely the parasitological nature of this stage. After proliferating, tachyzoites convert into bradyzoites, which are inside latent intracellular tissue cysts that form mainly in the muscles and brain. The formation of cysts is in part triggered by the pressure of the host immune system. The bradyzoites (also called "bradyzoic merozoites") are not responsive to antibiotics. Bradyzoites, once formed, can remain in the tissues for the lifespan of the host. In a healthy host, if some bradyzoites convert back into active tachyzoites, the immune system will quickly destroy them. However, in immunocompromised individuals, or in fetuses, which lack a developed immune system, the tachyzoites can run rampant and cause significant neurological damage.
The parasite's survival is dependent on a balance between host survival and parasite proliferation. T. gondii achieves this balance by manipulating the host's immune response, reducing the host's immune response, and enhancing the parasite's reproductive advantage. Once it infects a normal host cell, it resists damage caused by the host's immune system, and changes the host's immune processes. As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host's mitochondria and endoplasmic reticulum.
When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry organelle. These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT pathways to modulate the expression of cytokines at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. Additionally, certain strains of T. gondii can secrete a protein known as GRA15, activating the NF-κB pathway, which upregulates the pro-inflammatory cytokine IL-12 in the early immune response, possibly leading to the parasite's latent phase. The parasite's ability to secrete these proteins depends on its genotype and affects its virulence.
The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. To disrupt these proteins, T. gondii causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. T. gondii does not, however, cause downregulation of the pro-apoptosis effector proteins.
T. gondii also has the ability to initiate autophagy of the host's cells. This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang et al finds that infected cells lead to higher levels of autophagosomes in normal and infected cells. Their research reveals that T. gondii causes host cell autophagy using a calcium-dependent pathway. Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells.
The mechanisms above allow T. gondii to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of T. gondii per host cell cause a more severe effect. The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals.
T. gondii has been shown to produce a protein called GRA28, released by the MYR1 secretory pathway, which interferes with gene expression in infected cells and results in cells that behave like dendritic cells, becoming highly mobile in the body.
Since the parasite can change the host's immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats. This includes, but is not limited to, the responses to infections by Helicobacter felis, Leishmania major, or other parasites, such as Nippostrongylus brasiliensis.
Transmission
Toxoplasmosis is generally transmitted through the mouth when Toxoplasma gondii oocysts or tissue cysts are accidentally eaten. Congenital transmittance from mother to fetus can also occur. Transmission may also occur during the solid organ transplant process or hematogenous stem cell transplants.
Oral 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. Tissue cysts 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 unwashed fruit or vegetables that have been in contact with contaminated soil containing infected cat feces.