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Diagnostic testing for congenital toxoplasmosis.

The majority of infants with congenital toxoplasmosis have a normal physical examination at birth. Undiagnosed and untreated, however, nearly all of these babies will develop visual or neurologic impairments by adulthood. Thus, laboratory testing for this rare congenital infection in mother and baby raises important issues of diagnostic sensitivity, accuracy, and cost. The major diagnostic considerations for congenital toxoplasmosis involve: (1) identification and timing of infection in a pregnant woman; (2) determination of whether fetal infection has taken place prior to birth; (3) proving congenital infection after birth; and (4) adaptation of testing procedures to enable cost-effective mass screening of either pregnant women or newborn infants. A major point concerning diagnostic testing is that the tests available in many hospital-based and commercial laboratories frequently are misinterpreted or inaccurate. This concern is particularly true of indirect fluorescence tests for IgG and IgM antibodies and of enzyme-linked immunosorbent assay (ELISA) systems for quantitation of IgMspecific antibodies. The Food and Drug Administration has warned health care providers about this misinterpretation of IgM serologies and suggested guidelines for interpretation (Table). In general, all suspected infections should be confirmed in an experienced reference laboratory setting, such as the Palo Alto Medical Foundation (phone number: 650-853-4828.) Newer generation tests based on defined antigens, rather than whole organisms or lysates, may improve specificity and quantitation in the future. Except in very rare instances, only primary infection occurring during gestation or periconceptionally can lead to fetal infection. The problem of diagnosis of toxoplasmosis in a pregnant woman is complex because most pregnant women who acquire toxoplasmosis are asymptomatic, with a minority having cervical lymphadenopathy or a mononucleosis-like syndrome. Excisional biopsy may be helpful in diagnosis of selected cases, but antibody studies are required for most cases. Detection of IgG antibody creates the problem for the obstetrician of differentiating acute primary infection from long-standing latent infection. Screening for IgG antibodies generally is performed using indirect immunofluorescence or ELISA systems. Positive IgG indirect fluorescent antibody or ELISA tests are usually confirmed with a high titer ($1000) on the Sabin-Feldman dye test. Several tests are available to determine the acuity of maternal infection and include testing for Toxoplasma antibodies of IgM, IgA, or IgE classes. Acuity can also be determined by the use of the “differential agglutination” test or with recently developed tests for antibody avidity. These tests are available in the Palo Alto reference laboratory. The differential agglutination test is most useful for mothers with both IgG and IgM antibody positivity. In this test, the so-called AC antibody assay detects IgG response to acetone-fixed tachyzoites and is more likely to indicate acute stages of infection, while the HS assay tests CONCISE REVIEWS OF P E D I A T R I C I N F E C T I O U S D I S E A S E S T