Difference between revisions of "Toxoplasmosis - Human"

Latest revision as of 13:02, 20 July 2012

Introduction

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 oocysts in water or food contaminated by cat faeces, although consumption of undercooked meat containing tissue cysts also occurs. Contact with abortion products from infected ewes is 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 from AIDS. If initial infection occurs during pregnancy, or if cysts reactivate at this time, Toxoplasma may infect the foetus transplacentally. As most mothers are exposed to Toxoplasma gondii early in life, and are immunocompetent, transplacental infection is seen infrequently. Transmission via blood transfusions or organ transplantation can also occur in man.

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.

Clinical Signs

There are several manifestations of toxoplasmosis in man. Acute infection in healthy individuals is normally asymptomatic, but up to 20% of patients 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, myocarditis, high fevers or polymyositis, which may prove fatal without treatment.

When infection is acquired for the first time during pregnancy, congenital toxoplasmosis can arise. This may 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 occurred 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.

Indirect fluorescent antibody tests or an ELISA can be used to detect T. gondii-specific IgG and IgM antibodies. The production of these antibodies follows 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. Therefore, elevations in IgM alone indicates recent Toxoplasma gondii exposure, and an increased IgG with low IgM shows previous infection. In neonates, detection of specific IgM is consistent with congenital infection. This is because IgG crosses the placenta and could therefore come from an infected mother, but 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. Hands, kitchen utensils and work surfaces should all be washed with soap and water after contact with raw meat, and meat should not be tasted during cooking. As soil may be contaminated by 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. Pregnant women should also not assist at lambing.

There is no vaccine against toxoplasmosis in man.

Links

Ovine Toxoplasmosis

Feline and Canine Toxoplasmosis

Toxoplasmosis - Human Learning Resources
Literature Search Search for recent publications via CAB Abstract (CABI log in required)	Toxoplasmasis in humans publications

References

Beers, M H (2006) The Merck Manual of Diagnosis and Therapy (Eighteenth Edition), Merck.
Montoya, J and Liesenfeld, O (2004) Toxoplasmosis. Lancet, 363(9425), 1965-1976.
Sukthana, Y (2006) Toxoplasmosis: beyond animals to humans. Trends in Parasitology, 22(3), 137–142.
Toxoplasmosis Factsheets (2004) Centers of Disease Control and Prevention.

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-==Description==
+{{OpenPagesTop}}
+==Introduction==
-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.
+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 oocysts in water or food contaminated by cat faeces, although consumption of undercooked meat containing tissue cysts also occurs. Contact with abortion products from infected ewes is 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 from AIDS. If initial infection occurs during pregnancy, or if cysts reactivate at this time, ''Toxoplasma'' may infect the foetus transplacentally. As most mothers are exposed to ''Toxoplasma gondii'' early in life, and are immunocompetent, transplacental infection is seen infrequently. Transmission via blood transfusions or organ transplantation can also occur in man.
-''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==
-===Clinical Signs===
+There are several manifestations of toxoplasmosis in man. Acute infection in healthy individuals is normally asymptomatic, but up to 20% of patients 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.
-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.
+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, myocarditis, high fevers or polymyositis, which may prove fatal without treatment.
-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.
+When infection is acquired for the first time during pregnancy, congenital toxoplasmosis can arise. This may 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 occurred 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===
+==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.
-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.
+Indirect fluorescent antibody tests or an ELISA can be used to detect ''T. gondii''-specific IgG and IgM antibodies. The production of these antibodies follows 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. Therefore, elevations in IgM alone indicates recent ''Toxoplasma gondii'' exposure, and an increased IgG with low IgM shows previous infection. In neonates, detection of specific IgM is consistent with congenital infection. This is because IgG crosses the placenta and could therefore come from an infected mother, but IgM does not and must therefore be produced by the foetus itself.
-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 involving the CNS is suspected, CT and/or MRI may be used. One or more dense, rounded lesions may be seen.
-The diagnosis is usually made serologically using an indirect fluorescent antibody (IFA) test or enzyme immunoassay (EIA) for IgG and IgM antibodies. Specific IgM antibodies appear during the first 2 wk of acute illness, peak within 4 to 8 wk, and eventually become undetectable, but they may be present for as long as 18 mo after acute infection. IgG antibodies arise more slowly, peak in 1 to 2 mo, and may remain high and stable for months to years. Specific IgM antibodies with low IgG are consistent with recent infection in immunocompetent patients. Acute infection should also be suspected if the IgG is positive in an immunocompromised host with encephalitis. Toxoplasma-specific IgG antibody levels in AIDS patients with Toxoplasma encephalitis are usually low to moderate but may be absent; IgM antibodies are not present. Past infection in a healthy person typically produces a negative IgM test, and a positive IgG test. In patients with retinochoroiditis, low titers of IgG antibodies are usually present, but IgM antibodies are not detected.
+==Cytology==
+In the event of CNS toxoplasmosis, a CSF sample may show increased levels of protein and a lymphocytic pleocytosis.
-The diagnosis of acute toxoplasmosis during pregnancy and in the fetus or neonate can be difficult, and consultation with an expert is recommended. If the patient is pregnant and IgG and IgM are positive, an IgG avidity test should be done. High avidity antibodies in the first 12 to 16 wk of pregnancy essentially rules out an infection acquired during gestation. But a low IgG avidity result cannot be interpreted as indicating recent infection because some patients have persistent low IgG avidity for many months after infection. Suspected recent infection in a pregnant woman should be confirmed before intervention by having samples tested at a toxoplasmosis reference laboratory. If the patient has clinical illness compatible with toxoplasmosis but the IgG titer is low, a follow-up titer 2 to 3 wk later should show an increase in antibody titer if the illness is due to acute toxoplasmosis, unless the host is severely immunocompromised.
+==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.
-===Diagnostic Imaging===
+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. Hands, kitchen utensils and work surfaces should all be washed with soap and water after contact with raw meat, and meat should not be tasted during cooking. As soil may be contaminated by 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. Pregnant women should also not assist at lambing.
-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.
+There is no vaccine against toxoplasmosis in man.
-===Pathology===
+==Links==
-==Treatment==
+<big>'''[[Toxoplasmosis - Sheep|Ovine Toxoplasmosis]]
-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.
+'''[[Toxoplasmosis - Cat and Dog|Feline and Canine Toxoplasmosis]]</big>
-Potential organ donors should be tested to prevent the spread of the parasite through transplanted organs. Trimethoprim-sulfamethoxazole Some Trade Names
+*[http://www.cdc.gov/toxoplasmosis/ Center for Disease Control and Prevention: Toxoplasmosis Factsheets]
-may be used to prevent toxoplasmosis. People who cannot take this drug may be given pyrimethamine Some Trade Names
+*[http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1195733799638 Health Protection Agency: Toxoplasmosis]
-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
+{{Learning
-DARAPRIM
+|literature search = [http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=toxoplasmosis&occuring1=freetext&rowId=2&options2=AND&q2=human&occuring2=od&rowId=3&options3=AND&q3=&occuring3=freetext&x=34&y=5&publishedstart=yyyy&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all Toxoplasmasis in humans publications]
-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.
+==References==
+#Beers, M H (2006) '''The Merck Manual of Diagnosis and Therapy (Eighteenth Edition)''', ''Merck''.
+#Montoya, J and Liesenfeld, O (2004) Toxoplasmosis. ''Lancet'', '''363(9425)''', 1965-1976.
+#Sukthana, Y (2006) Toxoplasmosis: beyond animals to humans. ''Trends in Parasitology'', '''22(3)''', 137–142.
+#[http://www.dpd.cdc.gov/DPDx/HTML/Toxoplasmosis.htm Toxoplasmosis Factsheets] (2004) Centers of Disease Control and Prevention.
-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.
-==Prognosis==
-==Links==
-*[http://www.cdc.gov/toxoplasmosis/ Center for Disease Control and Prevention: Toxoplasmosis]
-==References==
+{{review}}
-#Beers, M H (2006) '''The Merck Manual of Diagnosis and Therapy (Eighteenth Edition)''', ''Merck''.
+{{OpenPages}}
-[[Category:Tissue_Cyst_Forming_Coccidia]][[Category:Zoonoses]]
+[[Category:Zoonoses]]
-[[Category:To_Do_-_Lizzie]]
+[[Category:Expert_Review]]