Introduction
Background
Toxoplasmosis is a disease caused by an obligate intracellular protozoal parasite, Toxoplasma gondii, whose name was derived from the crescent shape of the parasite (toxon is Greek for "arc"), as well as the name of the North African rodent in which it was first observed, Ctenodactylus gundi. T gondii is one of the most successful protozoal parasites; it infects the nucleated cells of virtually all warm-blooded animals. Some species of felines are the definitive host for sexual reproduction of the parasite; however, asexual reproduction occurs in secondary hosts, such as rodents, livestock, birds, and humans, culminating in the formation of tissue cysts, which persist for the lifespan of the secondary host.Human infection usually occurs via the oral or transplacental route. Consumption of raw or undercooked meat that contains viable tissue cysts (principally lamb and pork), direct ingestion of oocysts from contaminated soil and water, and consumption of unwashed vegetables are common sources of infection. Infection has also been reported in individuals who drink unpasteurized goat's milk.
Transplacental infection may occur if the mother acquires the parasite acutely or if a latent infection is reactivated during immunosuppression. Fetal infection usually occurs in the third trimester, but more severe sequelae may ensue if the fetus is contaminated in the first trimester.
It is important to differentiate patients with clinical infection from those who are simply seropositive for T gondii via exposure to toxoplasmosis. In adults, most T gondii infections are subclinical, but severe infection can occur in patients who are immunocompromised, such as those who have acquired immunodeficiency syndrome (AIDS) and malignancies. Affected organs include the gray and white matter of the brain, retinas, alveolar lining of the lungs (where the infection may mimic Pneumocystis carinii infection), heart, and skeletal muscle. AIDS-associated Toxoplasma encephalitis results from reactivation of chronic latent infection in more than 95% of patients. Congenital toxoplasmosis may be associated with anomalies such as microcephaly, microphthalmia, hydranencephaly, hydrocephalus secondary to aqueduct stenosis, porencephalic cyst, and periventricular calcification.
For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Brain Infection.
Pathophysiology
The T gondii organism is related to Plasmodium malariae and the Cryptosporidium, Isospora, and Sarcocystis species. These parasites form a group termed the coccidian parasites, which have a characteristic method of host transmission. The parasite can attach to any host cell in the body (except non-nucleated red blood cells [RBCs]), and they can become invaginated, forming a parasitophorous vacuole in which the organism resides.
In definitive hosts, such as cats and other members of the feline family, sexual reproduction of the parasite leads to infective oocyst development in the mammal’s intestinal lining. These oocysts are hardy and can survive in temperate climates in moist soil and without direct sunlight for up to 1 year. Infection may then occur when a secondary host (all other hosts including humans) ingests the oocysts.
After intestinal transit, parasitemia and widespread dissemination occur throughout the host’s body. This acute phase is followed by a latent phase during which encystation occurs in various tissues, particularly in the skeletal and cardiac muscles and in the brain. Once within the host tissue, asexual multiplication ensues. The asexual cycle occurs in 2 forms. In immunocompetent but nonimmune hosts, multiplication of tachyzoites — the trophozoite form of the organism that produces small cysts — is rapid, but replication slows with the development of host immunity. On the other hand, the bradyzoites divide slowly and remain dormant within the cysts. These tissue cysts are highly infective; when cats ingest mice with the cysts, the life cycle of the parasite is completed.
In immunocompetent hosts, cysts that contain the live T gondii organisms cause no harm; most patients remain asymptomatic but seropositive. However, if the immune system of the host declines, the cysts may reactivate, causing disseminated infection that manifests as encephalitis, myocarditis, or chorioretinitis. In immunocompromised patients, T gondii infection is potentially fatal. Seronegative patients can be infected via the usual oral route or via organ transplantation. More commonly, infection results from reactivation of latent tissue cysts.
Patients who have AIDS are at particular risk for developing disseminated toxoplasmosis, which more often manifests as central nervous system (CNS) abnormalities. As many as 50% of these patients who are seropositive for T gondii develop encephalitis. Toxoplasmosis is the most common cause of a focal brain lesion in patients with AIDS and frequently localizes to the basal ganglia , although other sites in the brain and spinal cord may be affected. A solitary focus may be seen in one third of patients, but multiple foci are seen more often. Histologic findings in CNS toxoplasmosis include inflammatory solid or cystic granulomas secondary to glial mesenchymal reaction, with surrounding edema and microinfarcts resulting from focal vasculitis. In AIDS-related Toxoplasma encephalitis, a well-circumscribed indolent granulomatous process or features of diffuse necrotizing encephalitis occur.
Frequency
United States
The prevalence of seropositive persons is 11-16% of the urban adult population. Annually, 3000 cases of congenital toxoplasmosis are reported.
International
It is estimated that 30-60% of the total human population is currently infected with the T gondii parasite.
In Europe, the highest prevalence of seropositive persons (90-95%) has been recorded in France, where undercooked or raw meat products are commonly consumed. Therefore, transplacental transmission is also highest in France; approximately 40 fetuses per 10,000 pregnancies are at risk. In Belgium, 50-80% of the population is infected compared with 20-40% in Britain. In Europe overall, congenital toxoplasmosis affects 1-10 in 10,000 newborn babies.
Mortality/Morbidity
- A study of 31 patients with congenital toxoplasmosis showed a clear relationship among the CNS lesions observed on computed tomography (CT) scans, neurologic deficit, and the date of maternal infection. CT scan findings in these infants are characteristic, depending on the timing of maternal infection — namely, was the mother infected and and did she undergo seroconversion before the 20th week of gestation, was she infected during weeks 20-30 of gestation, or was she infected and did she undergo seroconversion after the 30th week of gestation?
- Unfortunately, maternal treatment does not affect fetal outcome. Neonates who undergo shunt procedures that are performed to treat hydrocephalus, usually as a result of aqueduct stenosis, remain shunt dependent, and 20% of these patients require revision of the shunt over time. Neonatal hydrocephalus, extensive intracerebral calcification, and severe ocular involvement are poor prognostic indicators.
- Acute toxoplasmosis in patients who are immunocompromised can be a severe debilitating disease, particularly in those with CNS involvement, in whom the condition may be fatal. Drug therapy does not eradicate T gondii, and lifelong therapy to avoid relapse is often necessary in immunocompromised patients.
Sex
In France, more men than women are seropositive.
Presentation
In most adults, toxoplasmosis infection is subclinical, with seroconversion the only evidence. Occasionally, mild systemic disturbances may occur. In immunocompetent patients, the clinical presentation may mimic glandular fever with associated fatigue, chills, pyrexia, lymphadenopathy, and headaches. These symptoms may be more severe in immunocompromised patients. Uncommon manifestations include maculopapular rash, encephalomyelitis, myocarditis, and hepatitis.
Chorioretinitis is rare, occurring in fewer then 3% of patients with acute toxoplasmosis infection, but it may have serious sequelae, including blindness. AIDS-related CNS toxoplasmosis may present with neurologic deficits in 50-89% of affected patients and seizures in 15-25%, as well as altered mental status and, rarely, signs of increased intracranial pressure. Pulmonary symptoms rarely may dominate because of pulmonary infiltrates. Toxoplasmosis should always be considered in patients with AIDS who present with focal neurologic signs, particularly when associated with seizures, headaches, and fever. Congenital toxoplasmosis develops in approximately 40% of mothers who have a primary infection during pregnancy. The classic triad of congenital toxoplasmosis is chorioretinitis, hydrocephalus, and intracellular calcification. Most infants are severely ill, often with convulsions; only a few completely recover.
Preferred Examination
Magnetic resonance imaging (MRI) is considered superior to CT scanning in the detection of brain toxoplasmosis. The administration of intravenous (IV) contrast material with either modality improves the diagnostic yield and accuracy. However, ultrasound remains the pillar of intrauterine imaging.
Limitations of Techniques
Because patients who are immunocompromised are susceptible to a variety of opportunistic infections and malignancies, identifying a single cause that is responsible for the patient's symptoms is often difficult with imaging findings. However, because toxoplasmosis is a treatable condition, therapy is started immediately, and the scan is repeated in 1-2 weeks. A positive response to therapy is judged by the regression in size of all lesions.
Differential Diagnoses
Brain, Abscess
Brain, Lymphoma
Brain, Metastases
Other Problems to Be Considered
Fungal and other opportunistic infections
CNS lymphoma
CNS metastases
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Further Reading
Keywords
Toxoplasma gondii, T gondii, protozoal infection, parasitic infection, congenital toxoplasmosis, undercooked pork, undercooked lamb, raw meat, disseminated toxoplasmosis, acute toxoplasmosis, central nervous system toxoplasmosis, CNS toxoplasmosis, CNST
