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. Contact with abortion products from infected ewews is also a risk for pregnant women. 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, transmission via blood transfusions or organ transplantation can 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 as well as retinochoroiditis, cerebral calcifications, hydrocephalus/microcephaly, and psychomotor retardation. These last four signs together are characteristic of congenital toxoplasmosis. Infants infected during the third trimester are less severely affected and tend to appear normal at birth. However, signs may develop months to years later, and can include seizures, retinochoroiditis and intellectual disability.

Laboratory Tests

Changes in routine haematology and biochemistry may be seen in acute toxoplasmosis. These can include a mild anaemia and leukopenia, as well as increases in liver enzymes.

Detection of T. gondii-specific IgG and IgM antibodies by indirect fluorescent antibody tests or ELISA can be used for the diagnosis of human toxoplasmosis. The production of these antibodies follow different time courses: IgM appears in the first two weeks of infection, peaks at 4-8 weeks and declines over the following months, whereas IgG is produced more slowly and remains for months to years. This means that elevations in IgM with low IgG indicates recent Toxoplasma gondii exposure. An increased IgG with a low IgM shows previous infection in healthy individuals, and in neonates detection of specific IgM is consistent with congenital infection. This is because while IgG crosses the placenta (and could therefore come from an infected mother), IgM does not and must therefore be produced by the foetus itself.

Diagnostic Imaging

If toxoplasmosis involving the CNS is suspected, CT and/or MRI may be used. One or more dense, rounded lesions may be seen.

Cytology

In the event of CNS toxoplasmosis, a CSF sample may show increased levels of protein and a lymphocytic pleocytosis.

Treatment

Asymptomatic infections in immunocompetent patients do not require treatment. However, immunocompromised people, neonates and pregnant women are usually treated with sulfadiazine and pyrimethamine. Clindamycin can also be used.

From a veterinary perspective, the emphasis is on preventing human Toxoplasma gondii infection. Tissue cysts in meat are inactivated by thorough cooking and by freezing, so care should be taken that food is properly prepared. The hands of those handling meat, kitchen utensils and work surfaces should all be washed with soap and water after contact with raw meat. Meat should not be tasted during cooking. To minimise contact with potentially contaminated cat faeces, gloves should be worn whilst gardening, and vegetables should be washed before consumption. Pregnant women should avoid contact with cats; if this is not possible then they should at least avoid changing cat litter. Litter boxes should be covered and emptied daily, and cats should never be fed raw meat. Contact with infected ewes is a risk for pregnant women, and so they should not assist at lambing time.

There is no vaccine against toxoplasmosis in man.

Links

• Center for Disease Control and Prevention: Toxoplasmosis

References

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