Early neonatal diagnosis of congenital toxoplasmosis: value of comparative enzyme-linked immunofiltration assay immunological profiles and anti-Toxoplasma gondii immunoglobulin M (IgM) or IgA immunocapture and implications for postnatal therapeutic strategies

Abstract

Diagnostic strategies for congenital toxoplasmosis have changed profoundly in recent years. Immunological diagnostic methods, long considered disappointing, can now be used at a very early stage. Over a 3-year period, 1,050 infants at risk of congenital toxoplasmosis (born to 1,048 mothers infected during pregnancy) were monitored for a minimum of 12 months and a maximum of 7 years. More than 6,000 serum specimens were analyzed by comparative mother-infant immunological profiles (CIPs) based on an enzyme-linked immunofiltration assay (ELIFA) and an immunocapture method for the detection of specific immunoglobulin M (IgM) and IgA. IgG antibodies were also titrated. One hundred three cases of congenital toxoplasmosis were demonstrated. The CIP-ELIFA method had a better diagnostic yield (sensitivity, 90%) than specific IgM and/or IgA detection by immunocapture assay (sensitivity, 77%). By using a combination of these tests, congenital infection was diagnosed in the first month and the first 3 months of life in 90 and 94% of infants with toxoplasmosis, respectively, with a specificity of 99.8% and a positive predictive value of 99% at 8 months of age. This dual diagnostic approach (ELIFA and IgM-IgA immunocapture) is highly efficient and has important implications for therapy. Indeed, early postnatal diagnosis based on objective evidence enables therapy with pyrimethamine-sulfadoxine to be started immediately for 24 months, while spiramycin (which used to be given preventively for 9 to 12 months to all infants at risk) can be stopped after the first 3 months of life.

Value of Prenatal Diagnosis and Early Postnatal Diagnosis of Congenital Toxoplasmosis: Retrospective Study of 110 Cases

“…The fetal transmission rate was very high when seroconversion occurred during the third trimester, underlining the importance of early postnatal diagnosis in such cases, most of which escape antenatal diagnosis. IgM was detected by immunocapture in cord serum of 70% of the infected infants, and the combination of IgM and IgA immunocapture detection yielded the diagnosis in 80% of infected infants, a figure similar to those in other reports (4,13,19,40,47). Other investigators have achieved poor sensitivity (54%) of IgM detection at birth (22), although the specificity (91%) was similar to that observed in our study.…”

“…These data suggest that this analysis should be repeated during the first 2 months of life or later when all other tests are negative. Pinon et al (39,40) reported on the value of enzyme-linked immunofiltration assay (ELIFA) for comparison of maternal and newborn IgG and IgM patterns. Using the ELIFA method, those investigators detected, within 60 days of birth, 67, 64, and 82.5% of infections by comparing the maternal and newborn IgG, IgM, and IgG plus IgM profiles, respectively.…”

Population pharmacokinetics of pyrimethamine and sulfadoxine in children with congenital toxoplasmosis

“…At the beginning of the study (15 years ago), we discussed the protocol with our local ethics committee, who advised that written consent from a parent or guardian was not necessary. In collaboration with clinicians, we created the Reims Toxoplasmosis Group [1, 16], which managed the treatment of children with congenital toxoplasmosis (CT). Eighty‐nine children were monitored prospectively by regular clinical and laboratory measurements from birth until 13.9 years old.…”

Evaluation of DPC immulite 2000®Toxoplasma quantitative IgG/IgM kits for automated toxoplasmosis serology with immulite 2000®

“…It is therefore necessary to have reliable and specific serological techniques for assaying IgG and IgM, as definitive diagnosis of Toxoplasma acute infection is critical for the clinical management of the mother and her fetus (4). All the SC must be accompanied with early treatment for the mother and lead to screening for the infection in the infant, whether prenatal or postnatal (5)(6)(7)(8)(9). Postnatal screening is based (i) on examination of the placenta, (ii) on a serological examination of the newborn, requiring techniques that are particularly sensitive and specific, for which the results will condition the treatment of the infant to limit later sequelae (10)(11)(12).…”