| Toxoplasmosis | |
|---|---|
| Classification and external resources | |
T. gondii tachyzoites |
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| ICD-10 | B58 |
| ICD-9 | 130 |
| DiseasesDB | 13208 |
| MedlinePlus | 000637 |
| eMedicine | med/2294 |
| MeSH | D014123 |
Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii.[1] The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid (cat) family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself recently been infected, or by transmission from mother to fetus. Cats are the primary source of infection to human hosts, although contact with raw meat, especially pork, is a more significant source of human infections in some countries. Fecal contamination of hands is a significant risk factor.[2]
Up to one third of the world's human population is estimated to carry a Toxoplasma infection.[3] The Centers for Disease Control and Prevention notes that overall seroprevalence in the United States as determined with specimens collected by the National Health and Nutritional Examination Survey (NHANES) between 1999 and 2004 was found to be 10.8%, with seroprevalence among women of childbearing age (15 to 44 years) 11%.[4]
During the first few weeks post-exposure, the infection typically causes a mild flu-like illness or no illness. Thereafter, the parasite rarely causes any symptoms in otherwise healthy adults. However, those with a weakened immune system, such as AIDS patients or pregnant women, may become seriously ill, and it can occasionally be fatal. The parasite can cause encephalitis (inflammation of the brain) and neurologic diseases, and can affect the heart, liver, inner ears, and eyes (chorioretinitis). Recent research has also linked toxoplasmosis with brain cancer.[5]
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Infection has two stages:
During acute toxoplasmosis, symptoms are often influenza-like: swollen lymph nodes, or muscle aches and pains that last for a month or more. Rarely, a patient with a fully functioning immune system may develop eye damage from toxoplasmosis. Young children and immunocompromised patients, 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.
Swollen lymph nodes are commonly found in the neck or under the chin, followed by the axillae (armpits) and the groin. Swelling may occur at different times after the initial infection, persist, and/or recur for various times independently of antiparasitic treatment.[6] It is usually found at single sites in adults, but in children multiple sites may be more common. Enlarged lymph nodes will resolve within one to two months in 60% of patients. However, a quarter of patients take 2–4 months to return to normal and 8% take 4–6 months. A substantial number of patients (6%) do not return to normal until much later.[7]
It is easy for a host to become infected with Toxoplasma gondii and develop toxoplasmosis without knowing it. In most immunocompetent patients, the infection enters a latent phase, during which only bradyzoites are present, forming cysts in nervous and muscle tissue. Most infants who are infected while in the womb have no symptoms at birth but may develop symptoms later in life.[8]
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 μm by 2 μm , bow-shaped, 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.[9]
Studies have been conducted that show the toxoplasmosis parasite may affect behavior and may present as or be a causative or contributory factor in various psychiatric disorders such as depression, anxiety and schizophrenia.[10][11][12] In 11 of 19 scientific studies, T. gondii antibody levels were found to be significantly higher in individuals affected by first-incidence schizophrenia than in unaffected persons. Individuals with schizophrenia are also more likely to report a clinical history of toxoplasmosis than those in the general population.[13] Recent work at the University of Leeds has found that the parasite produces an enzyme with tyrosine hydroxylase and phenylalanine hydroxylase activity. This enzyme may contribute to the behavioral changes observed in toxoplasmosis by altering the production of dopamine, a neurotransmitter involved in mood, sociability, attention, motivation and sleep patterns. Schizophrenia has long been linked to dopamine dysregulation.[14]
Toxoplasmosis can be difficult to distinguish from that of primary central nervous system lymphoma, and as a result, the diagnosis is made by a trial of therapy (pyrimethamine, sulfadiazine + leucovorin), or a brain biopsy if the drugs produce no effect.
Detection of Toxoplasma gondii in human blood samples may also be achieved by using the polymerase chain reaction (PCR).[15] Inactive cysts may exist in a host which would evade detection.
Toxoplasmosis cannot be detected with immunostaining. Lymph nodes affected by toxoplasma have characteristic changes, including poorly demarcated reactive germinal centers, clusters of monocytoid B cells and scattered epithelioid histiocytes.
Transmission may occur through:
Cats excrete the pathogen in their feces for a number of weeks after contracting the disease, generally by eating an infected rodent. Even then, cat faeces are not generally contagious for the first day or two after excretion, after which the cyst 'ripens' and becomes potentially pathogenic.[18]
Congenital toxoplasmosis is a special form in which an unborn child is infected via the placenta. A positive antibody titer indicates previous exposure and immunity and largely ensures the unborn baby's safety. A simple blood draw at the first pre-natal doctor visit can determine whether or not the woman has had previous exposure and therefore whether or not she is at risk. If a woman receives her first exposure to toxoplasmosis while pregnant, the baby is at particular risk. A woman with no previous exposure should avoid handling raw meat, exposure to cat feces, and gardening (cat feces are common in garden soil). Most cats are not actively shedding oocysts and so are not a danger, but the risk may be reduced further by having the litterbox emptied daily (oocysts require longer than a single day to become infective), and by having someone else empty the litterbox. However, while risks can be minimized, they cannot be eliminated. For pregnant women with negative antibody titer, indicating no previous exposure to T. gondii, as frequent as monthly serology testing is advisable as treatment during pregnancy for those women exposed to T. gondii for the first time decreases dramatically the risk of passing the parasite to the fetus.
Despite these risks, pregnant women are not routinely screened for toxoplasmosis in most countries (Portugal,[19] France,[20] Austria,[20] Uruguay,[21] and Italy[22] being the exceptions) for reasons of cost-effectiveness and the high number of false positives generated. As invasive prenatal testing incurs some risk to the fetus (18.5 pregnancy losses per toxoplasmosis case prevented),[20] postnatal or neonatal screening is preferred. The exceptions are cases where fetal abnormalities are noted, and thus screening can be targeted.[20]
Some regional screening programmes operate in Germany, Switzerland and Belgium.[22]
Treatment is very important for recently infected pregnant women, to prevent infection of the fetus. Since a baby's immune system does not develop fully for the first year of life, and the resilient cysts that form throughout the body are very difficult to eradicate with anti-protozoans, an infection can be very serious in the young.
Treatment is often only recommended for people with serious health problems or with HIV with CD4 count under 200, because the disease is most serious when one's immune system is weak. Trimethoprim/sulfamethoxazole is the drug of choice to prevent Toxoplasma, but is not the drug to treat.
Medications that are prescribed for acute toxoplasmosis are:
(Other antibiotics such as minocycline have seen some use as a salvage therapy).
In people with latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics do not reach the bradyzoites in sufficient concentration.
Medications that are prescribed for latent toxoplasmosis are:
The parasite itself can cause various effects on the host body, some of which are not fully understood.
It has been found that the parasite has the ability to change the behaviour of its host: infected rats and mice are less fearful of cats—in fact, some of the infected rats seek out cat-urine-marked areas. This effect is advantageous to the parasite, which is able to proliferate if a cat eats the infected rat and thereby becomes a carrier.[25] The mechanism for this change is not completely understood, but there is evidence that toxoplasmosis infection raises dopamine levels and concentrates in the amygdala in infected mice.[26]
The findings of behavioural alteration in rats and mice have led some scientists to speculate that Toxoplasma may have similar effects in humans. Toxoplasma is one of a number of parasites that may alter their host's behaviour as a part of their life cycle.[27]
The evidence for behavioral effects on humans is controversial.[28] No prospective research has been done on the topic, e.g., testing people before and after infection to ensure that the proposed behavior arises only afterwards. Although some researchers have found potentially important associations with Toxoplasma, the causal relationship, if any, is unknown, i.e., it is possible that these associations merely reflect factors that predispose certain types of people to infection. However, many of the neurobehavioral symptoms that are postulated to be due to toxoplasmosis correlate to the general function of dopamine in the human brain, and the fact that toxoplasma encodes the dopamine synthetic enzyme tyrosine hydroxylase enzymes makes it likely that neurobehavioral symptoms can result from infection.[29]
These types of studies are suggestive but cannot confirm a causal relationship (because of the possibility, for example, that schizophrenia increases the likelihood of Toxoplasma infection rather than the other way around).[30]
The U.S. NHANES (1999–2004) national probability sample found that 10.8% of U.S. persons 6–49 years of age, and 11.0% of women 15–44 years of age, had Toxoplasma-specific IgG antibodies, indicating that they were infected with the organism.[4] This prevalence has significantly decreased from the NHANES III (1988–1994).[31][32]
Two risk factors for contracting toxoplasmosis are:
A University of California, Davis study of dead sea otters collected from 1998 to 2004 found that toxoplasmosis was the cause of death for 13% of the animals.[33] Proximity to freshwater outflows into the ocean was a major risk factor. Ingestion of oocysts from cat faeces is considered to be the most likely ultimate source.[34] Runoff containing wild cat faeces and litter from domestic cats flushed down toilets are possible sources of oocysts.[35] According to an article in New Scientist[36] the parasites have been found in dolphins and whales. Researchers Black and Massie believe that anchovies, which travel from estuaries into the open ocean, may be helping to spread the disease.
The protozoan was first discovered by Nicolle & Manceaux, who in 1908 isolated it from the African rodent Ctenodactylus gundi, then in 1909 differentiated the disease from Leishmania and named it Toxoplasma gondii.[20] The first recorded congenital case was not until 1923, and the first adult case not until 1940.[20] In 1948, a serological dye test was created by Sabin & Feldman, which is now the standard basis for diagnostic tests.[37]
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