False-positive results in immunoglobulin M (IgM) toxoplasma antibody tests and importance of confirmatory testing: the Platelia Toxo IgM test

Abstract

Although tests for detection of immunoglobulin M (IgM) toxoplasma antibodies have been reported to have a high degree of accuracy, it is well recognized by investigators in the United States and Europe that false-positive results may occur with many of these tests, at times to an alarming degree. Unfortunately, this information is not well documented in the literature. Studies on various toxoplasma IgM test kits are frequently flawed. The investigators often use reference tests which have not previously been carefully evaluated as well as sera that were not appropriate to answer the question of how often false-positive results might occur. We recently had the unique opportunity to evaluate the accuracy of the Platelia Toxo IgM test in 575 serum samples obtained during an outbreak of toxoplasmosis which occurred in 1995 in the Capital Regional District of British Columbia, Canada. When compared with results obtained in a reference IgM enzyme-linked immunosorbent assay (ELISA), the Platelia Toxo IgM test had a sensitivity of 99.4%, specificity of 49.2%, positive predictive value of 51.9%, negative predictive value of 99.3%, and an overall agreement of 67.0%. In an attempt to resolve discrepancies between these two tests, a serological profile (Sabin-Feldman dye test, IgA and IgE antibody tests, differential agglutination [AC/HS] test, and IgG avidity method) was performed. Of 153 serum samples that were positive in the Platelia Toxo IgM test and negative in the IgM ELISA, 71 (46.4%) were negative in the Sabin-Feldman dye test. Of the serum samples that were positive in the dye test, 77 (93.9%) had a serological profile most compatible with an infection acquired in the distant past. These results reveal high numbers of false-positive results in the Platelia Toxo IgM test and highlight the importance of appropriate evaluation of commercial tests that are currently being marketed. Our results also emphasize the importance of confirmatory testing to determine whether the results of an IgM antibody test reflect the likelihood of a recently acquired infection.

Evaluation of a commercial IgE ELISA in comparison with IgA and IgM ELISAs, IgG avidity assay and complement fixation for the diagnosis of acute toxoplasmosis

“…In regular external laboratory quality control surveys, they yield qualitative results comparable to products of other (mostly international) companies [26]. In the present study, IgM was the most sensitive assay, at the expense of low specificity [9] and a low positive predictive value caused by long-term endurance of IgM. Generally, IgM is still interpreted as being associated directly with acute toxoplasmosis, and even low-level IgM may provoke inappropriate interventions, especially in the case of pregnant women.…”

“…Nevertheless, a high percentage of positive results after a number of years may be distorted by the fact that some patients monitored (for periods of up to 14 years) may have had a problematic decline in antibody levels following toxoplasmosis. In most published studies, an evaluation of diagnostic tests is based on a comparison with reference methods (e.g., the survey of 18 studies evaluating IgM ELISA, summarised by Liesenfeld et al [9]). However, the true motivation for testing is not to determine whether patients have anti-Toxoplasma IgM, but whether they are suffering from acute toxoplasmosis.…”

Detection of anti-Toxoplasma immunoglobulin M in pregnant women

“…Thus it is of great importance for the clinical microbiologist to know perfectly well the performance of the kit he or she uses. This can be ascertained only by carrying out comparative studies with previously described tests, even if none of the techniques is the absolute reference since there is no real "gold standard" for IgM detection, as specified by Liesenfeld et al (1,2). A World Health Organization reference serum exists for IgG, but not for IgM (3).…”

A case of congenital toxoplasmosis whose mother demonstrated serum low IgG avidity and positive tests for multiplex‐nested PCR in the amniotic fluid

“…Serological tests for detection of IgM antibodies are commonly performed for the diagnosis of acute acquired T. gondii infection. However, it is well recognized that false‐positive results may occur with many of these tests, 12 and that T. gondii IgM antibodies may persist for many months or even years following the acute infection 13,14 . These complicate the appropriate interpretation of a positive T. gondii IgM result, especially in pregnant women.…”

“…These complicate the appropriate interpretation of a positive T. gondii IgM result, especially in pregnant women. Therefore, to determine whether the positive IgM result reflects the likelihood of a recently acquired infection, confirmatory testing by additional tests such as IgG avidity or by the demonstration of a significant rise in antibody titers in serial serum samples should be performed during pregnancy 12,15 . T. gondii IgG avidity assay has been developed for the serological diagnosis of acute acquired infection, and this measures the antigen‐binding avidity of T. gondii ‐specific IgG antibodies.…”