Toxoplasmosis - Human

Description

Toxoplasmosis is the disease caused by Toxoplasma gondii, an intracellular protozoan parasite of warm-blooded mammals and birds. The cat is the definitive host of Toxoplasma gondii, and all other species, including man, are intermediate hosts.

T. gondii has three infectious stages: 1) sporozoites; 2) actively reproducing tachyzoites; and 3) slowly multiplying bradyzoites. Tachyzoites and bradyzoites are found in tissue cysts, whereas sporozoites are containted within oocysts, which are excreted in the faeces. This means that the protozoa can be transmitted by ingestion of oocyst-contaminated food or water, or by consumption of infected tissue. In naive cats, Toxoplasma gondii undergoes an enteroepithelial life cycle. Cats ingests intermediate hosts containing tissue cysts, which release bradyzoites in the gastrointestinal tract. The bradyzoites penetrate the small intestinal epithelium and sexual reproduction ensues, eventually resulting the production of oocysts. Oocysts are passed in the cat's faeces and sporulate to become infectious once in the environment. These can then be ingested by other mammals, including humans.

When man or another animal ingests oocysts or tissue cysts, T. gondii intiates extraintestinal replication. This process is the same for all intermediate hosts, although the form ingested depends on diet. Sporozoites (from oocysts) or bradyzoites (from tissue cysts) are released in the intestine to infect the intestinal epithelium where they replicate. This produces tachyzoites, which reproduce asexually within the infected cell. When the infected cell ruptures, tachyzoites are released and disseminate via blood and lymph to infect other tissues. Tachyzoites then replicate intracellularly again, and the process continues until the host becomes immune or dies. If the infected cell does not burst, tachyzoites eventually encyst as bradyzoites and persist for the life of the host, most commonly in the brain or skeletal muscle.

Human exposure to toxoplasmosis is common: it is estimated that aroung 60% of healthy adults worldwide are seropositive to Toxoplasma gondii. The most common route of human infection is ingestion of oocyts in water or food contaminated by cat faeces, although consumption of undercooked meat containing tissue cysts also occurs. An immune response occurs in response to infection, and tissue cysts form in several organs. These cysts may later reactivate in immunocompromised patients, for example those suffering AIDs. If initial infection occurs during pregnancy, or if cysts reactivate at this time, Toxoplasma may infect a foetus transplacentally. As most mothers are exposed to Toxoplasma gondii early in life, and are immunocompetent, transplacental infection is seen infrequently. In man, blood transfusions and organ trasplantation can also occur.

Despite the various methods of transmission to man, and the high seroprevalence to Toxoplasma gondii, the risk of developing cloinical disease is low and is generally restricted to foetuses infected in utero, and immunosuppressed patients.

Signalment

Despite the various methods of transmission to man, and the high seroprevalence to Toxoplasma gondii, the risk of developing clinical disease is low and is generally restricted to foetuses infected in utero, and immunosuppressed patients such as those infected with Human Immunodeficiency Virus.

Diagnosis

Clinical Signs

There are several manifestations of toxoplasmosis in man. Acute infection in healthy individuals is normally asymptomatic, but up to 20% of patient develop lymphadenopathy. This is sometimes accompanied by flu-like signs which may include pyrexia, pharyngitis and myalgia and last for several weeks before a full recovery is made.

CNS signs are the most common presentation in immunocompromised patients suffering Toxoplasma infection or re-activation. Signs are due to intracranial mass lesions or encephalitis, and can include headaches, seizures, pyrexia, coma and focal neurological deficits. Ocular involvement is also possible and usually results from re-activation of a congenital infection. Inflammation of the choroid causes pain and visual disturbances. Occasionally, in severely immunocompromised patients, disease can be seen outwith the CNS and the eye. In these incidences, affected tissues and therefore clinical signs can be variable. For example, patients may suffer pneumonitis, myocarditism, high fevers or chills and polymyositis. Unless treated, these disseminated infections may be fatal.

When infection is acquired for the first time during pregnancy, congenital toxoplasmosis can arise. This nmay also occur if a mother infected before conception becomes immunosuppressed during pregnancy. Foetuses infected congenitally may be aborted, stillborn, or born with toxoplasmosis. Infections later in gestation are more likely to give rise to a live but infected neonate. When neonates are born with toxoplasmosis disease can be severe, particularly if transplacental infection occured early in pregnancy. Signs can include rashes, icterus and hepatosplenomegaly, and there are four abnormalities that are characteristic of congenital toxoplasmosis: retinochoroiditis, cerebral calcifications, hydrocephalus/microcephaly, and psychomotor retardation. Prognosis is poor. Many children with less severe infections and most infants born to mothers infected during the 3rd trimester appear healthy at birth but are at high risk of seizures, intellectual disability, retinochoroiditis, or other symptoms developing months or even years later.

mmune system dysfunction (eg, people infected with human immunodeficiency virus). In these individuals, toxoplasmosis usually presents as meningoencephalitis and results from the emergence of T gondii from tissue cysts located in the brain as immunity wanes rather than from primary T gondii infection. Toxoplasmosis is also a major concern for pregnant women because tachyzoites can migrate transplacentally and cause birth defects in human fetuses.

people with a healthy immune system have few symptoms and recover fully. Children born with congenital toxoplasmosis may be severely ill and die shortly after birth, or they may have no symptoms until months or years later. Some never become ill. Typical symptoms in newborns can include inflammation of the eyes (chorioretinitis), which can result in blindness, as well as enlargement of the liver and spleen, jaundice, rash, easy bruising, seizures, a large or small head, and mental retardation.

Toxoplasmosis acquired after birth in people with a healthy immune system seldom causes symptoms. When symptoms occur, they are usually mild and include swollen but painless lymph nodes, intermittent low fevers, a vague ill feeling, and sometimes a sore throat. Some people develop only chorioretinitis, with blurred vision, eye pain, and sensitivity to light. Chorioretinitis usually results from reactivation of congenital toxoplasmosis.

Symptoms of toxoplasmosis in people with a weakened immune system depend on the site of infection. Toxoplasmosis of the brain (encephalitis) produces symptoms such as weakness on one side of the body, trouble speaking, headache, confusion, seizures, and coma. Acute disseminated toxoplasmosis can cause a rash, high fever, chills, trouble breathing, and fatigue. In some people, infection causes inflammation of the liver (hepatitis), lungs (pneumonitis), or heart (myocarditis). The affected organ may stop functioning adequately (called organ failure). These types of toxoplasmosis can be life threatening.

Laboratory Tests

The diagnosis is usually based on blood tests that detect antibodies against the parasite. However, if the person's immune system is impaired by AIDS, the blood test may be falsely negative. To determine whether a fetus has been infected, a doctor usually takes a sample of the fluid around the fetus (amniotic fluid) to be analyzed.

acute Atypical lymphocytosis, mild anemia, leukopenia, and slightly elevated liver enzymes are common. The syndrome may persist for weeks but is almost always self-limited.

Diagnostic Imaging

If toxoplasmosis of the brain is suspected, computed tomography (CT) or magnetic resonance imaging (MRI) of the brain is done. Less commonly, a piece of infected tissue is removed and examined under a microscope (biopsy) to identify parasites or characteristic proteins (antigens) released by the parasite.

Treatment

Pregnant women should avoid contact with cats. If contact is unavoidable, pregnant women should at least avoid cleaning cat litter boxes or wear gloves when doing so. Meat should be cooked thoroughly, to a temperature of 165 to 170° F (74 to 77° C), and hands should be washed thoroughly after handling raw meat, soil, or cat litter. Freezing to a temperature of 9° F (13° C ) or below also destroys the parasite.

Potential organ donors should be tested to prevent the spread of the parasite through transplanted organs. Trimethoprim-sulfamethoxazole Some Trade Names may be used to prevent toxoplasmosis. People who cannot take this drug may be given pyrimethamine Some Trade Names DARAPRIM with dapsone Some Trade Names ACZONE . Another option is atovaquone Some Trade Names MEPRON with or without pyrimethamine Some Trade Names DARAPRIM . Because pyrimethamine Some Trade Names DARAPRIM can damage bone marrow, leucovorin is given with it to help protect the bone marrow. People with AIDS may be given highly active antiretroviral drugs to reduce the risk of toxoplasmosis.

Infected adults without symptoms and with a healthy immune system do not require treatment. Adults with symptoms and infants with congenital toxoplasmosis are treated with sulfadiazine plus pyrimethamine Some Trade Names DARAPRIM and leukovorin. Higher does of pyrimethamine Some Trade Names DARAPRIM are typically used in people with AIDS or other conditions that weaken the immune system. If people cannot take sulfadiazine, clindamycin Some Trade Names CLEOCIN can be used with pyrimethamine Some Trade Names DARAPRIM instead. Women who acquire toxoplasmosis during pregnancy may be treated with spiramycin to prevent transmission to the fetus. In addition to these drugs, people with chorioretinitis are given prednisone or another corticosteroid to reduce inflammation. In people with AIDS, toxoplasmosis tends to recur, so drugs are often continued indefinitely.

To prevent infection, the hands of people handling meat should be washed thoroughly with soap and water after contact, as should all cutting boards, sink tops, knives, and other materials. The stages of T gondii in meat are killed by contact with soap and water. T gondii organisms in meat can also be killed by exposure to extreme cold or heat. Tissue cysts in meat are killed by heating the meat throughout to 67°C or by cooling to -13°C. Toxoplasma in tissue cysts are also killed by exposure to 0.5 kilorads of gamma irradiation. Meat of any animal should be cooked to 67°C before consumption, and tasting meat while cooking or while seasoning should be avoided. Pregnant women should avoid contact with cat litter, soil, and raw meat. Pet cats should be fed only dry, canned, or cooked food. The cat litter box should be emptied daily, preferably not by a pregnant woman. Gloves should be worn while gardening. Vegetables should be washed thoroughly before eating because they may have been contaminated with cat feces. At present there is no vaccine to prevent toxoplasmosis in humans.

Links

• Center for Disease Control and Prevention: Toxoplasmosis

References

1. Beers, M H (2006) The Merck Manual of Diagnosis and Therapy (Eighteenth Edition), Merck.