Toxoplasmosis is caused by a protozoan organism, Toxoplasma gondii. About 30%-50% (range, 3%-70%) of the U.S. population is reported to have serologic evidence of past infection. The disease is transmitted in some cases via raw or poorly cooked meat but in many cases by oocysts in feces of infected cats. The cats shed oocysts for 7-20 days after infection. The oocysts may remain infective in soil for over a year. There is also a possibility of infection from contact with cat litter box contents while the cat is shedding oocysts. Once ingested, the organisms encyst in various tissues, particularly in muscle, and remain dormant for many years or for the life of the host. Initial infection in children or adults produces clinical disease in about 10% (range, 10%-20%) of cases, usually in the form of lymphadenopathy of varying extent. There is a congenital form of clinical disease and an acquired form. The congenital form of toxoplasmosis occurs when T. gondii organisms are transmitted to the fetus through the placenta when the mother acquires active Toxoplasma infection near the time of conception or during pregnancy (infection several weeks or more before conception will not injure the fetus). Maternal acute infection during the first trimester infects 14% of fetuses; during the second trimester, 29%; and during the third trimester, 59%. One report found the highest incidence of severe fetal infections resulted from first trimester maternal infection and the least in third trimester infection. About 90% of mothers acutely infected during pregnancy are asymptomatic. Congenital toxoplasmosis is manifested most often by chorioretinitis (usually bilateral), which sometimes does not become manifest until teenage or young adulthood. Other frequent findings include brain damage (mental retardation, microcephalus or hydrocephalus, and convulsions) and intracerebral calcifications on x-ray film. Cerebrospinal fluid (CSF) is abnormal in about two thirds of patients, showing xanthochromia, mononuclear pleocytosis, and elevated protein levels (i.e., the findings usually associated with aseptic meningitis). Less frequently there is an acute neonatal disease with fever, hepatosplenomegaly, and cerebral symptoms that are clinically similar to bacterial septicemia. The more severe acute and chronic clinical disorders are more common when the mother is infected early in pregnancy, whereas infection later in pregnancy is more likely to result in symptoms (e.g., mental retardation) that are not manifest until after the neonatal period. Acquired toxoplasmosis is usually seen in older children or adults. The most common manifestations are either asymptomatic lymphadenopathy or a viral type of illness with lymphadenopathy, low-grade fever, malaise, and possibly other symptoms.

There may (or may not) be some atypical lymphocytes, and the clinical picture may suggest “heterophil-negative” infectious mononucleosis, cytomegalovirus infection, other viral infections or even malignant lymphoma. Another type of acquired infection is associated with deficient immunologic defense mechanisms, due to either immunologic suppression therapy or a disease such as leukemia or acquired immunodeficiency syndrome (AIDS). This is actually a reactivation of previous latent Toxoplasma infestation. Cerebral infection occasionally is the first manifestation of AIDS. Overall, Toxoplasma infects the central nervous system (CNS) in 12%-31% of patients with AIDS and comprises 25%-80% of CNS infections in AIDS.

Diagnosis

Diagnosis requires isolation of the organisms or serologic tests for antibody formation. Culture has proved to be very difficult, and most laboratories are not equipped to do it. Tissue culture is positive in about 40% of cases. In one study, culture sensitivity was only 25%. Mouse inoculation is a form of culture method and is positive in up to 70% of cases. Lymph node biopsy frequently can suggest the diagnosis by showing small groups of histiocytes that involve germinal centers, although the pattern is not specific enough for definitive diagnosis. Histologic slides rarely show organisms in lymph nodes.

Serologic tests form the backbone of diagnosis. The indirect fluorescent antibody (IFA) procedure is the most commonly used present-day serologic procedure. The IFA test detects the same antibody as the Sabin-Feldman methylene blue dye test, which was the original standard test for toxoplasmosis. The dye test, however, required working with live Toxoplasma organisms. The IFA procedure can be used to detect either IgM or IgG antibody. It is somewhat better in detection of IgG than IgM.

The IFA-IgM antibody titer begins to rise about 7-10 days after infection, reaches a peak at about 8 weeks (range, 4-10 weeks) and usually becomes nondetectable 6-12 months after infection. In one study, 20% were still detectable at 12 months. High titers of IgG antibody may cause false negative IgM results. If the IgG can be separated from the IgM, the false negative reaction can be avoided. The presence of rheumatoid factor or antinuclear antibody may produce false positive results. False positive results may also be found on tests of some newborns with other congenital infections. If the IgG can be separated from the IgM, the false positive reaction can be eliminated.

The IFA-IgG antibody titer begins to rise about 4-7 days after the IgM antibody; reaches a peak in about 8 weeks (range, 4-10 weeks), and begins to fall slowly in about 6 months. Low titers usually persist for many years. Antinuclear antibody may produce false positive results.

Rise in titer of either IgM or IgG antibody to Toxoplasma is rapid, with considerable elevation occurring by the end of 1 week. Therefore, a low titer of IgM or IgG usually means old rather than recent infection in patients with maternal or congenital infection. However, when ocular infection is seen as an isolated finding in older children or adults, titers frequently are not high because the initial infection was congenital. Therefore, it may be difficult to tell whether the ocular disease is due to toxoplasmosis or to something else. This is made more difficult because exposure to Toxoplasma infection is very common.

An indirect hemagglutination (IHA) test that detects only IgG antibody is used in some laboratories. It is used mainly to see if a newly pregnant woman has antibody against Toxoplasma, thus suggesting immunity to infection.

Enzyme-linked immunosorbent assay (ELISA) methods detecting IgM, IgG, or both, as well as other methods such as latex agglutination (LA), are commercially available. Evaluations in general show 85%-100% sensitivity compared to IFA in older children and adults and 30%-77% in newborns. However, there is significant variation in different kits. Nucleic acid probes with polymerase chain reaction (PCR) amplification have also been reported.

In immunosuppressed patients with serious toxoplasma infection, the infection often is reactivated from previous but dormant infection. In these cases, unfortunately, antibody does not increase in response to the reactivation.

Interpretation of toxoplasma serologic results

If a woman is pregnant and it is desirable to know if she is immune to Toxoplasma infection, a negative titer means that she is susceptible to infection. A low titer of IgG (<1:1000) or the presence of IHA antibodies usually means that she had the disease at some time in the past and is immune. Since there is a small chance that a very early infection could be present and the titer is just beginning to rise, an IFA-IgM test can then be done. If the IFA-IgM antibody titer is greatly elevated but the IFA-IgG antibody titer is still low, this indicates early acute infection with the IgG antibody just starting to rise. Alternatively, an additional specimen may be drawn 7-10 days later and retested for IFA-IgG antibody. A fourfold rising titer indicates acute infection. A stable low titer means no recent infection. If the original specimen contains a high titer of IFA-IgG or IHA antibodies, the problem is difficult. The infection could be either acute or recent (within 1-2 years) but not acute. Only the acute infection is dangerous to the fetus. A high IgM titer is suggestive of recent infection, but in some cases it may persist for several weeks or months, falsely suggesting a more recent infection. On the other hand, it may fall rapidly and thus can be negative in association with a high IFA-IgG titer, even though acute infection began only a few weeks before.

In a newborn with possible congenital toxoplasmosis, most investigators believe that an elevated IgM level would support the diagnosis (although other infections can also produce IgM response). The IFA-IgG titer may be considerably elevated, but IgG antibody can cross the placenta; thus, maternal IgG antibody can appear in the fetal circulation if the mother has an elevated titer from either old or recent infestation. Therefore, to make a diagnosis of congenital toxoplasmosis, it is necessary to demonstrate a rising IgG titer in the infant. If no active infant infection is present and antibody is only passively acquired from the mother, the infant IgG titer, instead of rising, should fall by the sixth week as the maternally acquired antibody is gradually eliminated.