 |
Toxoplasmosis is infection with Toxoplasma gondii. Symptoms range from none to benign lymphadenopathy (a mononucleosis-like illness) to life-threatening CNS disease or involvement of other organs in immunocompromised people. Retinochoroiditis, seizures, and intellectual disability occur in congenital infection. Diagnosis is by serologic tests, histology, or PCR. Treatment is most often with pyrimethamine plus either sulfadiazine or clindamycin. Corticosteroids are given concurrently for retinochoroiditis.
Human exposure to toxoplasmosis is common wherever cats are found; 20 to 40% of healthy adults in the US are seropositive. The risk of developing disease is very low except for a fetus infected in utero and people who are or become immunocompromised.
Pathophysiology
T. gondii is ubiquitous in birds and mammals. This obligate intracellular parasite invades and multiplies asexually as tachyzoites within the cytoplasm of any nucleated cell (see Fig. 2: Extraintestinal Protozoa: Toxoplasma gondii life cycle. ). When host immunity develops, multiplication of tachyzoites ceases and tissue cysts form; cysts persist in a dormant state for years, especially in brain and muscle. The dormant Toxoplasma forms within the cysts are called bradyzoites. Sexual reproduction of T. gondii occurs only in the intestinal tract of cats; the resultant oocysts passed in the feces remain infectious in moist soil for months.
Infection can occur by
Ingestion of oocysts in food or water contaminated with cat feces is the most common mode of oral infection. Infection can also occur by eating raw or undercooked meat containing tissue cysts, most commonly lamb, pork, or rarely beef. After ingestion of oocysts or tissue cysts, tachyzoites are released and spread throughout the body. This acute infection is followed by the development of protective immune responses and the formation of tissue cysts in many organs. The cysts can reactivate, primarily in immunocompromised patients. Toxoplasmosis reactivates in 30 to 40% of AIDS patients who are not taking antibiotic prophylaxis, but the widespread use of trimethoprim/sulfamethoxazole for Pneumocystis prophylaxis has dramatically reduced the incidence.
Toxoplasmosis can be transmitted transplacentally if the mother becomes infected during pregnancy or if immunosuppression reactivates a prior infection. Transmission of Toxoplasma to a fetus is extraordinarily rare in immunocompetent mothers who have had toxoplasmosis earlier in life. Transmission may occur via transfusion of whole blood or WBCs or via transplantation of an organ from a seropositive donor. In otherwise healthy people, congenital or acquired infection can reactivate in the retina. Past infection confers resistance to reinfection.
Symptoms and Signs
Infections may manifest in several ways:
Acute toxoplasmosis:
Acute infection is usually asymptomatic, but 10 to 20% of patients develop bilateral, nontender cervical or axillary lymphadenopathy. A few of these also have a mild flu-like syndrome of fever, malaise, myalgia, hepatosplenomegaly, and less commonly, pharyngitis, which may mimic infectious mononucleosis. Atypical lymphocytosis, mild anemia, leukopenia, and slightly elevated liver enzymes are common. The syndrome may persist for weeks but is almost always self-limited.
CNS toxoplasmosis:
Most patients with AIDS or other immunocompromised patients who develop toxoplasmosis due to reactivation present with ring-enhancing intracranial mass lesions or encephalitis. These patients typically have headache, altered mental status, seizures, coma, fever, and sometimes focal neurologic deficits, such as motor or sensory loss, cranial nerve palsies, visual abnormalities, and focal seizures.
Congenital toxoplasmosis:
This type results from a primary, often asymptomatic infection acquired by the mother during pregnancy. Women infected before conception ordinarily do not transmit toxoplasmosis to the fetus unless the infection is reactivated during pregnancy by immunosuppression. Spontaneous abortion and stillbirth may occur. The percentage of surviving fetuses born with toxoplasmosis depends on when maternal infection is acquired; it increases from 15% during the 1st trimester to 30% during the 2nd to 60% during the 3rd.
Disease in neonates may be severe, particularly if acquired early in pregnancy; symptoms include jaundice, rash, hepatosplenomegaly, and the characteristic tetrad of abnormalities: bilateral retinochoroiditis, cerebral calcifications, hydrocephalus or microcephaly, and psychomotor retardation. Prognosis is poor.
Many children with less severe infections and most infants born to mothers infected during the 3rd trimester appear healthy at birth but are at high risk of seizures, intellectual disability, retinochoroiditis, or other symptoms developing months or even years later.
Ocular toxoplasmosis:
This type usually results from congenital infection that is reactivated, often during the teens and 20s, but rarely, it occurs with acquired infections. Focal necrotizing retinitis and a secondary granulomatous inflammation of the choroid occur and may cause ocular pain, blurred vision, and sometimes blindness. Relapses are common.
Disseminated infection and non-CNS involvement:
Disease outside the eye and CNS is much less common and occurs primarily in severely immunocompromised patients. They may present with pneumonitis, myocarditis, polymyositis, diffuse maculopapular rash, high fevers, chills, and prostration. In toxoplasmic pneumonitis, diffuse interstitial infiltrates may progress rapidly to consolidation and cause respiratory failure, whereas endarteritis may lead to infarction of small lung segments. Myocarditis, in which conduction defects are common but often asymptomatic, may rapidly lead to heart failure. Untreated disseminated infections are usually fatal.
Diagnosis
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 immunocompromised patients 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.
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.
In general, detection of specific IgM antibody in neonates suggests congenital infection. Maternal IgG crosses the placenta, but IgM does not. Detection of Toxoplasma-specific IgA antibodies is more sensitive than IgM in congenitally infected infants, but it is available only at special reference facilities (eg, Palo Alto Medical Foundation [telephone 650-853-4828]). They should be consulted when fetal or congenital infection is suspected.
Toxoplasma are occassionally demonstrated histologically. Tachyzoites, which are present during acute infection, take up Giemsa or Wright's stain but may be difficult to find in routine tissue sections. Tissue cysts do not distinguish acute from chronic infection. Toxoplasma must be distinguished from other intracellular organisms, such as Histoplasma, Trypanosoma cruzi, and Leishmania. PCR tests for parasite DNA in blood, CSF, or amniotic fluid are available at several reference laboratories. PCR-based analysis of amniotic fluid is the preferred method to diagnose toxoplasmosis during pregnancy.
If CNS toxoplasmosis is suspected, patients should have head CT with contrast agent, MRI, or both plus a lumbar puncture if there are no signs of increased intracranial pressure. MRI is more sensitive than CT. CSF may show lymphocytic pleocytosis and elevated protein levels. CT typically shows single or multiple dense, rounded, ring-enhancing lesions. Although these lesions are not pathognomonic, their presence in patients with AIDS and CNS symptoms warrants a trial of chemotherapy for T. gondii. If the suspected diagnosis of toxoplasmosis is correct, clinical or radiographic improvement should become evident within 7 to 14 days. If symptoms persist, a brain biopsy should be considered.
Treatment
Most immunocompetent patients do not require therapy unless visceral disease is present or severe symptoms persist. However, specific treatment is indicated for acute toxoplasmosis of neonates, pregnant women, and immunocompromised patients.
The most effective regimen in immunocompetent patients is pyrimethamine plus sulfadiazine. Dosage for pyrimethamine is 50 to 100 mg po q 12 h for 1 day, then 25 to 100 mg once/day for 3 to 4 wk in adults (1 mg/kg q 12 h for 3 days, then 1 mg/kg once/day for 4 wk in children; maximum 25 mg/day). Dosage for sulfadiazine is 1 to 1.5 g po qid for 3 to 4 wk in adults (25 to 50 mg/kg qid for 4 wk in children). Higher doses of pyrimethamine are used in HIV-infected patients with CNS toxoplasmosis. Some clinicians use a loading dose of pyrimethamine 200 mg the first day, then 50 to 100 mg/day plus sulfadiazine for 4 to 6 wk. In patients who have or develop sulfonamide hypersensitivity, clindamycin 600 to 800 mg po tid is given instead of sulfonamides. Another option is atovaquone 1500 mg q 12 h plus pyrimethamine, starting with a 200-mg loading dose followed by 75 mg/day for 6 wk. Relapses of toxoplasmosis are common in patients with AIDS, and suppressive treatment should continue indefinitely unless the CD4 count increases and remains above 200/μL. Pyrimethamine bone marrow suppression can be minimized with leucovorin (also called folinic acid; not folate, which blocks the therapeutic effect). The dosage is 10 to 25 mg po once/day. Patients with ocular toxoplasmosis should also be given corticosteroids.
Treatment of pregnant women with primary infection can decrease the incidence of fetal infection. Spiramycin 1 g po tid or qid has been used safely to reduce transmission in pregnant women during the 1st trimester (available from the FDA [telephone 301-827-2335]), but spiramycin is less active than pyrimethamine plus sulfonamide and does not cross the placenta. Spiramycin is continued until fetal infection is documented or excluded at the end of the 1st trimester. If no transmission has occurred, spiramycin can be continued to term. If the fetus is infected, pyrimethamine plus sulfadiazine is used. Pyrimethamine is a potent teratogen and should not be used during the 1st trimester. Consultation with an infectious diseases expert is recommended.
Congenitally infected infants should be treated with pyrimethamine every 2 to 3 days and with sulfadiazine once/day for about a year. Infants should also receive leucovorin while receiving pyrimethamine and for 1 wk after pyrimethamine is stopped to prevent bone marrow suppression.
Prevention
Washing hands thoroughly after handling raw meat, soil, or cat litter is essential. Food possibly contaminated with cat feces should be avoided. Meat should be cooked to 165 to 170° F.
Chemoprophylaxis is recommended for patients with HIV and a positive IgG T. gondiiserologic test once CD4+ cell counts are < 100/μL. One double-strength tablet of trimethoprim/sulfamethoxazole once/day, which also is prophylactic against Pneumocystis jirovecii, is one regimen. Alternatively, pyrimethamine plus dapsone or atovaquone with or without pyrimethamine can be used.
Last full review/revision December 2009 by Richard D. Pearson, MD
Content last modified February 2012
| |
|
