Microbiology and Epidemiology

Toxoplasmosis is caused by the intracellular parasite Toxoplasma gondii; cats and their prey are the definitive hosts. The primary route of transmission to humans is ingestion of tissue cysts from soil, food (e.g., undercooked meat), or water contaminated by cat feces.

• Roughly one-third of women who contract T. gondii during pregnancy transmit the parasite to the fetus, with a 65% risk of transmission if maternal infection is acquired in the third trimester.
• In the United States and most European countries, seroconversion rates increase with age and exposure. In the United States in 2009-2010, 13.2% of individuals >6 years old had serologic evidence of exposure; rates are higher in most other regions of the world.

Pathogenesis

Both humoral and cellular immunity are important, but subclinical infection commonly persists for the pt's lifetime. Immunocompromised hosts lack factors required to control infection; the consequences are progressive focal destruction and organ failure.

Clinical Manifestations

Disease in immunocompetent hosts is usually asymptomatic (80-90% of cases) and self-limited and does not require therapy. In contrast, immunocompromised pts, including newborns, can develop severe infections typically involving the CNS.

• In the minority of immunocompetent pts who develop symptoms of acute infection, cervical lymphadenopathy is the most common finding; nodes are nontender and discrete. Generalized lymphadenopathy, fever <40°C (<104°F), headache, malaise, and fatigue occur in 20-40% of pts. Clinical disease usually resolves within several weeks, although lymphadenopathy may persist for several months.
• Immunocompromised pts develop acute toxoplasmosis through reactivation of latent infection in 95% of cases; the remainder of cases are due to new acquisition of parasites.
  • CNS findings include encephalopathy, meningoencephalitis, and mass lesions. Pts may develop changes in mental status (75%), fever (10-72%), seizures (33%), headaches (56%), and focal neurologic findings (60%). The brainstem, basal ganglia, pituitary gland, and corticomedullary junction are most often involved.
• Multiple organs (e.g., lungs, GI tract, skin, eyes, heart, liver) can be affected.
  • - Toxoplasmapneumonia is often confused with Pneumocystis pneumonia because of an overlapping pt population and similar clinical presentations (i.e., fever, dyspnea, and nonproductive cough rapidly progressing to respiratory failure).
• Congenital infection, which affects 400-4000 infants each year in the United States, may initially be asymptomatic but can result in reactivation and clinical disease (e.g., chorioretinitis) decades later.
• Toxoplasma causes ∼35% of all cases of chorioretinitis in the United States and Europe. Blurred vision, macular involvement with loss of central vision, scotoma, photophobia, and eye pain are manifestations of infection. On examination, yellow-white cotton-like patches with indistinct margins of hyperemia are seen. Older lesions appear as white plaques with distinct borders and black spots.

Diagnosis

Culture of the parasite is difficult and can be done only at specialized laboratories. Serology is the primary method of diagnosis.

• Results of IgM, IgG, and antibody avidity assays can be combined to help determine when infection may have occurred. (Of note, IgM can persist for >1 year.) These tests, along with a more extensive panel of serologic tests, can be performed at the Toxoplasma Serology Laboratory at the Palo Alto Medical Foundation (www.pamf.org/serology/clinicianguide.html).
• In immunocompromised pts, a presumptive clinical diagnosis can be based on clinical presentation, history of exposure (e.g., a positive IgG result), and radiologic evaluation. Radiologic studies demonstrate bilateral contrast-enhancing lesions, typically in the basal ganglia and corticomedullary junction. These lesions can be difficult to distinguish from CNS lymphoma, although the latter more frequently consists of only a single lesion. A brain biopsy may be required for definitive diagnosis.
• Congenital toxoplasmosis is diagnosed by PCR of amniotic fluid (to detect the B1 gene of the parasite) and by the persistence of IgG antibody or a positive IgM titer after the first week of life; IgG antibody determinations should be repeated every 2 months.
• Ocular toxoplasmosis is diagnosed by the detection of typical lesions on ophthalmologic examination and the demonstration of a positive IgG titer in serum.

Chemoprophylaxis

The risk of disease is very high among AIDS pts who are seropositive for T. gondii and have a CD4+ T lymphocyte count of <100/µL. TMP-SMX (one double-strength tablet daily) should be given to these pts as prophylaxis against both Pneumocystis pneumonia and toxoplasmosis. Primary or secondary prophylaxis can be stopped if, after institution of antiretroviral treatment, the CD4+ T lymphocyte count remains >200/µL for 3 months.

Personal Protection Measures

Toxoplasma infection can be prevented by the avoidance of undercooked meats and oocyst-contaminated materials (e.g., a cat's litter box).